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Continued examination of the stem bark of Newbouldia laevis afforded three minor phenylethanoid glycosides, designated as newbouldiosides D – F. Their structures were elucidated by spectroscopic methods as β-(3,4-dihydroxyphenyl)ethyl 5-O-syringoyl-β-D-apiofuranosyloxy-(1 → 2)-O-[α-L-rhamnopyranosyl-(1 → 3)]-6-O-E-sinapoyl-β-D-glucopyranoside, β-(3,4-dihydroxyphenyl)ethyl β-D-apiofuranosyloxy-(1 → 2)-O-[α-L-rhamnopyranosyl-(1 → 3)]-6-O-E-sinapoyl-β-D-glucopyranoside, and β-(3,4-dihydroxyphenyl)ethyl β-D-apiofuranosyloxy-(1 → 2)-O-α-L-rhamnopyranosyl-(1 → 2)-6-O-E-sinapoyl-β-D-glucopyranoside, respectively. These metabolites are the first members possessing a sinapoyl structural element. In addition, the series of naturally occurring flavonoids is extended by the identification of 3′,4′,5,7-tetrahydroxy-5′-methoxyflavanone and apigenin-5-O-α-L-rhamnopyranosyl-7-O-β-D-glucopyranoside obtained from leaf extracts of Markhamia zanzibarica and aromadendrin-7-O-(2″-O-formyl)-β-D-glucopyranoside isolated from Spathodea campanulata. The latter compound is the first example of a flavonoid possessing a formylated glucosyl moiety.

Introduction Craterostigma plantagineum and Lindernia brevidens are resurrection plants, so these plants can tolerate desiccation of their vegetative tissues. Different components and mechanisms contribute to desiccation tolerance and secondary plant metabolites, like phenolic compounds, may play a role during these processes. Objectives Secondary plant metabolites of the two resurrection plants, C. plantagineum and L. brevidens as well as the closely related desiccation sensitive species, L. subracemosa, were investigated regarding the polyphenol profile. Material and methods Secondary plant compounds were extracted with acidified methanol and analysed with ultra-high-performance liquid chromatography electrospray ionisation mass spectrometry (UHPLC-ESI-MS). Phenolic compounds were identified by comparing of ultraviolet (UV) and MSn -spectra with published data. All compounds were quantified as verbascoside equivalents by external calibration at the compound specific wavelength. Results In total, eight compounds that belong to the subclass of phenylethanoid glycosides and one flavone, luteolin hexoside pentoside, were identified. Two of these compounds exhibited a fragmentation pattern, which is closely related to phenylethanoid glycosides. The predominantly synthesised phenylethanoid in all of the three plant species and in every stage of hydration was verbascoside. The total content of phenolic compounds during the three stages of hydration, untreated, desiccated, and rehydrated revealed differences especially between C. plantagineum and L. brevidens as the latter one lost almost all phenolic compounds during rehydration. Conclusion The amount of verbascoside correlates with the degree of desiccation tolerance and verbascoside might play a role in the protective system in acting as an antioxidant.

Phenylethanoid glycosides (PhGs) are generally water‐soluble phenolic compounds that occur in many medicinal plants. Until June 2020, more than 572 PhGs have been isolated and identified. PhGs possess antibacterial, anticancer, antidiabetic, anti‐inflammatory, antiobesity, antioxidant, antiviral, and neuroprotective properties. Despite these promising benefits, PhGs have failed to fulfill their therapeutic applications due to their poor bioavailability. The attempts to understand their metabolic pathways to improve their bioavailability are investigated. In this review article, we will first summarize the number of PhGs compounds which is not accurate in the literature. The latest information on the biological activities, structure–activity relationships, mechanisms, and especially the clinical applications of PhGs will be reviewed. The bioavailability of PhGs will be summarized and factors leading to the low bioavailability will be analyzed. Recent advances in methods such as bioenhancers and nanotechnology to improve the bioavailability of PhGs are also summarized. The existing scientific gaps of PhGs in knowledge are also discussed, highlighting research directions in the future.

Background: The genus Verbascum is well documented for its antioxidant potential but Verbascum sinaiticum is comparatively less studied plant. The current study was carried out to search for antioxidant nutraceuticals from this species. Objective: To explore the antioxidant potential of Verbascum sinaiticum and to identify its active constituents. Methods: The methanolic extract of air-dried aerial part of the Verbascum sinaiticum was partitioned with hexane, chloroform and ethyl acetate. The water-soluble part of ethyl acetate afforded six phenylethanoid glycosides by repeated chromatography over Sephadex LH-20, silica gel and ODS columns. Antioxidant activity of solvent extracts and isolated constituents were evaluated by DPPH, ABTS and FRAP assays. Results: Six phenylethanoid glycosides was isolated and characterized as Verbascoside, Eukovoside, Martynoside, Jionoside D, Campneoside I and Campneoside II, from the most active fraction. Conclusion: Verbascum sinaiticum demonstrated prospective antioxidant activity. The watersoluble part of EtOAc (WSEAE) was found the most active extract whereas Verbascoside was identified as the most potent constituent. All isolated compounds exhibited significant antioxidant activity whereas their synergistic effect was found prominent in the parent fraction.

Context Fruit of Avicennia marina (Forsk.) Vierh. (Acanthaceae) is used as a Chinese herb. Studies have found that it contains marinoid J, a novel phenylethanoid glycoside (PG) compound, but its neuroprotective functions are largely unknown. Objective This study evaluated the effects of marinoid J on vascular dementia (VD) and determined its potential mechanisms of action. Materials and methods The VD model was established by the ligation of the bilateral common carotid artery in Sprague–Dawley rats, who received daily intragastrically administration of saline, marinoid J (125 or 500 mg/kg body weight/d), or oxiracetam (250 mg/kg body weight/d) for 14 days (20 rats in each group). The Morris water maze (MWM) was used to evaluate cognitive performance. The hippocampus was subjected to histological and proteomic analyses. Results Marinoid J shortened the escape latency of VD rats (31.07 ± 3.74 s, p

Osteoarthritis (OA) is a complex disease, source of pain and disability that affects millions of people worldwide. OA etiology is complex, multifactorial and joint-specific, with genetic, biological and biomechanical components. Recently, several studies have suggested a potential adjuvant role for natural extracts on OA progression, in terms of moderating chondrocyte inflammation and following cartilage injury, thus resulting in an overall improvement of joint pain. In this study, we first analyzed the phenylethanoid glycosides profile and the total amount of polyphenols present in a leaf aqueous extract of Verbascum thapsus L. We then investigated the anti-inflammatory and anti-osteoarthritic bioactive potential of the extract in murine monocyte/macrophage-like cells (RAW 264.7) and in human chondrocyte cells (HC), by gene expression analysis of specifics inflammatory cytokines, pro-inflammatory enzymes and metalloproteases. Six phenylethanoid glycosides were identified and the total phenolic content was 124.0 ± 0.7 mg gallic acid equivalent (GAE)/g of extract. The biological investigation showed that the extract is able to significantly decrease most of the cellular inflammatory markers, compared to both control cells and cells treated with Harpagophytum procumbens (Burch.) DC. ex Meisn, used as a positive control. Verbascum thapsus leaf aqueous extract has the potential to moderate the inflammatory response, representing an innovative possible approach for the inflammatory joint disease treatment.

As the sixth-largest Angiosperm family, Lamiaceae contains more than 245 genera and 7886 species that are distributed worldwide. It is also the third-largest family based on the number of taxa in Turkey where it is represented by 46 genera and 782 taxa with a high endemism ratio (44%). Besides, Lamiaceae are rich in plants with economic and medicinal value containing volatile and nonvolatile compounds. Many aromatic plants of Lamiaceae such as Salvia, Sideritis, Stachys, Phlomis, and Teucrium species are used in traditional herbal medicine throughout Turkey as well as in other Mediterranean countries. Salvia (Sage tea “Adaçayı”), Sideritis (Mountain tea “Dağçayı”), Stachys (Hairy Tea “Tüylü Çay”), and Phlomis (Turkish sage “Çalba or Şalba”) are the largest genera that are used as herbal teas. This review focuses on the volatile and nonvolatile compounds of Lamiaceae from the genera Phlomis and Eremostachys of the subfamily Lamioideae with emphasis on iridoids, phenylethanoid glycosides, and essential oils.

Inspired by dried blood spots (DBS), “dried spots of herbal medicines” (DSHM) concept was proposed here. In response to this superior sampling means, a new platform integrating dried spot, serially coupled reversed phase liquid chromatography and hydrophilic interaction liquid chromatography (RPLC-HILIC), and tandem mass spectrometry (MS/MS), was configured for directly, comprehensively chemical profiling of HM-derived liquid matrices. As an important original source of Cistanches Herba (Chinese name: Roucongrong) that is a well-known tonic HM, Cistanche sinensis (Csi) was employed to illustrate and validate the applicability. Dried spots (I.D. 3.0 mm) were prepared by loading 2 μL aliquots of Csi extract onto filter paper. Each dried spot was packed into an in-line filter holder (I.D. 3.0 mm × 4.0 mm) and then inserted behind the auto-sampler of a well-defined instrumentation named RPLC-HILIC–MS/MS. Hybrid ion trap-time of flight MS and hybrid triple quadrupole-linear ion trap MS were deployed in combination for the in-depth MS/MS data acquisition of diverse chemical families, such as phenylethanoid glycosides, lignans, iridoids, amino acids, and so forth. To assist chemical profiling, an in-house chemical library was built by collecting as much prior knowledge as possible. A total of 88 components were detected and tentatively annotated in Csi by matching their multi-stage MS spectra with those of authentic standards and literature data. Collectively, DSHM carried all merits of DBS, and the integrative dried spot-RPLC-HILIC-MS/MS platform was a promising analytical tool for direct chemical analysis and rapid quality evaluation of HMs, in particular those traditional Chinese medicine injections.

Introduction Over the last decades, the demand of medicinal plants has vastly increased. The health trend and social changes are leading to a growing demand for herbal products, as medicines and in particular as food supplements. Various cultivations of medicinal plants have been developed in order not only to respond on this enormous market, but also to offer high-quality products. Cultivated plants have attracted great scientific interest for their rich and high standard chemical compositions. Objective Our study focuses on the phytochemical profile of cultivated Sideritis euboea Heldr., a shrub with a great commercial value. The whole isolation course of all extracts, fractions and sub-fractions was continuously monitored and traced down using an NMR strategy, which permitted their detail characterisation and enabled us to choose the more abundant extract. Methods Aerial parts of cultivated S. euboea were extracted with solvents of increasing polarity and their secondary metabolites were identified by NMR analyses. Results So far, using various analytical methods, 16 secondary metabolites have been isolated from the methanol extract; two iridoids, seven flavones, five phenylethanoid glucosides and two phenolic acids. In addition to the previous investigation of the wild population, the present study revealed that its chemical profile is similar and even richer in phenolic compounds. Conclusion The metabolic profile of cultivated S. euboea was studied through 1 H-NMR spectra; the structures of the isolated secondary metabolites were assigned based on their one-dimensional and two-dimensional NMR spectra. The NMR strategy allowed us to detect even the minor compounds in the extracts.

Five new compounds, a flavonol glycoside ( 1), a megastigmane ( 2), 2 cyclohexylethanoids ( 3, 4), and a phenylethanoid derivative ( 5), together with 15 known compounds ( 6– 20) including flavonoid glycosides, cyclohexylethanoids, and phenolic compounds, have been isolated from Cornus sanguinea drupes. All the structures have been determined by 1D and 2D NMR spectroscopic analysis and mass spectrometry data. The antioxidant capability of the most representative isolated compounds was evaluated in the hydrogen peroxide (H2O2)-induced premature cellular senescence model of human dermal and gingival fibroblasts. Several derivatives counteracted the increase of reactive oxigen species (ROS) production in both cellular models. Among the most promising, compounds 8, 14, and 20 were able to counteract cell senescence, decreasing the expression of p21 and p53. Furthermore, compound 14 decreased the expression of inflammatory cytokines (IL-6) in both cell models and counteracted the decrease of collagen expression induced by the H2O2 in dermal human fibroblasts. These data highlight the anti-aging properties of several isolated compounds from C. sanguinea drupes, supporting its possible use in the cure of skin or periodontitis lesions.

Chromatographic purification of the alcoholic extract from the aerial parts of the Saudi plant Nuxia oppositifolia (Hochst.), Benth., resulted in five isolated phenolic compounds. Two flavones, hispidulin (1) and jaceosidin (2), and the phenylethanoid glycosides, verbascoside (3), isoverbascoside (4), and conandroside (5), were identified and their chemical structures were determined by spectroscopic analyses. The insecticidal activity of compounds 1 and 2, in addition to 11 compounds isolated in a previous research (6–16), was evaluated against the Yellow Fever mosquito, Aedes aegypti. Four compounds displayed adulticidal activity with LD50 values of 2–2.3 μg/mosquito. Free radical scavenging properties of the plant extracts and compounds (1–5) were evaluated by measuring the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate radical cation (ABTS•+) scavenging activity. All compounds exhibited notable activity, compared with the positive control, l-Ascorbic acid. This study suggests that N. oppositifolia could be a promising source of secondary metabolites, some with lethal adulticidal effect against Ae. aegypti.

Previously phytochemical investigations carried out on the flowers and trunk bark extracts of Citharexylum spinosum L. tree, allowed the isolation of twenty molecules belonging to several families of natural substances [triterpene acids, iridoid glycosides, phenylethanoid glycosides, 8,3'-neolignan glycosides, together with other phenolic compounds]. In the present work, a biological evaluation (anti-tyrosinase, anticholinesterase and cytotoxic activities) was performed on the prepared extracts and the isolated secondary metabolites. The results showed that the EtOAc extract of the trunk bark displayed the highest anti-tyrosinase effect with a percent inhibition of 55.0 +/- 1.8% at a concentration of 100 mu g/mL. The highest anticholinesterase activity was presented by the same extract with an IC50 value of 99.97 +/- 3.01 mu g/mL. The EtOAc extract of flowers and that of the trunk bark displayed the best cytotoxic property with IC50 values of 96.00 +/- 2.85 and 88.75 +/- 2.00 mu g/mL, respectively, against the human cervical cancer cell line (HeLa), and IC50 values of 188.23 +/- 3.88 and 197.00 +/- 4.25 mu g/mL, respectively, against the human lung cancer (A549) cell lines. Biological investigation of the pure compounds showed that the two 8,3'-neolignan glycosides, plucheosides D-1-D-2, generate the highest anti-tyrosinase potency with a percent inhibition of 61.4 +/- 2.0 and 79.5 +/- 2.3%, respectively, at a concentration of 100 mu M. The iridoid glycosides exhibited a significant anticholinesterase activity with IC50 values ranging from 17.19 +/- 1.02 to 52.24 +/- 2.50 mu M. Triterpene pentacyclic acids and iridoid glycosides exerted encouraging cytotoxic effects against HeLa with IC50 values ranging from 9.00 +/- 1.10 to 25.00 +/- 1.00 mu M. The study of the structure-activity relationship (SAR) has been sufficiently and widely discussed. The natural compounds that exhibited the significant bioactivities were docked.

Ligustri Lucidi Fructus (LLF) is a traditional Chinese medicine to treat osteopathic and hepatic diseases. Wine steaming is the major processing method for LLF in Chinese Pharmacopoeia, but the chemical changes involved are still unclear. In this study, a research strategy was proposed to reveal the chemical changes during wine steaming processing of LLF. Firstly, in total 104 compounds were tentatively identified using UHPLC/Orbitrap-MS. Secondly, potential chemical changes were revealed by comparing the peak areas of the 104 compounds between LLF and the corresponding wine-steamed LLF (WLLF). The results indicated that iridoid and phenylethanoid esters were readily hydrolyzed during wine steaming processing, while organic acids, flavonoids, and triterpenes were stable. Finally, 7 selected compounds were simultaneously determined in 21 batches of LLF/WLLF samples using a 10-min UPLC/UV method. The contents of 4 esters decreased from 3.64% to 2.71%, and the contents of 3 potential hydrolysis products increased from 0.27% to 0.88% after processing. Our study indicated that hydrolysis of iridoid and phenylethanoid esters such as specneuzhenide was responsible for the chemical changes during the wine processing of LLF. The proposed strategy could be employed to investigate the chemical changes of other herbs during processing.

Qu-feng-sheng-shi Granules (QFSSG), a common prescription for the treatment of chronic inflammation and allergic rhinitis, is widely used in the clinic as a traditional Chinese medicine. Chemical analysis and quality control studies of this formulation are relatively limited compared with pharmacological studies. In this study, a high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q/TOF-MSn ) was used to identify the components in this prescription. Next, to quantify six major compounds, an HPLC-UV method was developed and validated. The results showed that 53 compounds were identified based on the MSn data, retention time and previous reports, including 17 coumarins, 14 lignans, 10 chromones, nine phenylethanoid glycosides and three other compounds, were identified or tentatively assigned. Contents of six major bioactive compounds (4'-O-β-glucopyranosyl-5-O-methylvisamminol, Prim-O-glucosylcimifugin, forsythin, magnolin, imperatorin, isoimperatorin) could be determined by HPLC simultaneously. In addition, the potential anti-inflammatory activity of six major compounds was determined too, and we found that four compounds (4'-O-β-glucopyranosyl-5-O-methylvisamminol, Prim-O-glucosylcimifugin, forsythin, imperatorin) have a potent nitric oxide inhibitory effect. In conclusion, this work provided comprehensive information on the quality control of QFSSG and evaluated the potential biological activity of the main components in QFSSG, which can contribute to understanding and using it more scientifically.

Phenylethanoid glycosides (PhGs) are compounds made of phenylethyl alcohol, caffeic acid and glycosyl moieties. The first published references about phenylethanoid glycosides concerned the isolation of echinacoside from Echinaceu ungustifolia (Asteraceae) in 1950 and verbascoside from Verbascum sinuatum (Scrophulariaceae) in 1963. Over the past 60 years, many compounds with these structural characteristics have been isolated from natural sources, and most of these compounds possess significant bioactivities, including antibacterial, antitumor, antiviral, anti-inflammatory, neuro-protective, antioxidant, hepatoprotective, and immunomodulatory activities, among others. In this review, we will summarize the phenylethanoid glycosides described in recent papers and list all the compounds that have been isolated over the past few decades. We will also attempt to present and assess recent studies about the separation, extraction, determination, and pharmacological activity of the excellent natural components, phenylethanoid glycosides.

Three new acylated phenylethanoid glycosides, kurroaosides A (14), B (15), and C (16), and a new acylated cucurbitane-type triterpene glycoside, kurroaoside D (17), were isolated from a methanol extract of the rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) along with 29 known isolates including 10 acylated phenylethanoid glycosides (18–27), three cucurbitane-type triterpene glycosides (32–34), and a nortriterpene glycoside (35). The structures of these new compounds (14–17), including their stereochemistry, were determined based on chemical and physicochemical evidence derived from NMR and MS analysis. Among the isolates, acylated iridoid glycosides, picrosides I (8), II (9), III (10), and IV (11) and 6-feruloylcatalpol (12), phenylethanoid glycosides (14–16), triterpene glycosides, cucurbitacin B 2-O-β-D-glucopyranoside (32) and 25-acetoxy-2-β-D-glucopyranosyloxy-3,16,20-trihydroxy-9-methyl-19-norlanosta-5-en-22-one (35), and an acetophenone glycoside, picein (36), significantly promoted collagen synthesis at 10–30 μM, with no cytotoxicity being observed at the effective concentrations. Furthermore, acylated phenylethanoid glycosides, calceolarioside A (19, IC50 = 69.2 μM), plantamajoside (20, 51.8 μM), isoplantamajoside (21, 76.8 μM), and scroside E (23, 65.5 μM), exhibited collagenase inhibitory activity equivalent to that of positive agents caffeic acid (75.6 μM) and epigallocatechin 3-O-gallate (75.4 μM).

Ethnopharmacological relevance Callicarpa kwangtungensis, as a characteristic traditional herb in China, has been widely used as indigenous medicine for thousands of years in the treatment of upper respiratory tract infection, tonsillitis, pneumonia and traumatic bleeding in China. Phenylethanoid glycosides (PhGs), as natural polyphenols, are especially abundant in this herb and can be regarded as the representative active ingredients in C. kwangtungensis. Aim of this study This study was performed to investigate the anti-inflammatory pharmacodynamic basis of six PhGs (acteoside, forsythoside B, poliumoside, alyssonoside, parvifloroside A, and syringalide A 3′-α-L-rhanmnopyranoside) isolated from C. kwangtungensis from the perspective of antioxidation. Materials and methods Six PhGs were isolated from the anti-inflammatory extracts of C. kwangtungensis by various chromatographic techniques and their anti-inflammatory activity on RAW 264.7 murine macrophages induced by LPS was investigated by measuring the release of tumor necrosis factor (TNF-α), the colonic interleukin-6 (IL-6), nitric oxide (NO) and reactive oxygen species (ROS). Further, the underlying anti-inflammatory mechanism of two PhGs (forsythoside B and alyssonoside) was explored by determining the expression of Kelch-like ECH-association protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (OH-1) and quinone oxidoreductase 1 (NQO1). Besides, molecular simulation was also employed to evaluate the binding capacity of two PhGs with Keap1. Results Compared with the model group, six PhGs revealed obviously inhibitory effects on TNF-α, IL-6, NO and the generation of ROS in RAW 264.7 macrophages. Moreover, forsythoside B and alyssonoside could act as the inhibitors of Keap1-Nrf2 interaction, then activated the nuclear translocation of Nrf2 and promoted the upregulated protein expression of HO-1 and NQO1, finally suppressed LPS-induced inflammatory response in RAW 264.7 macrophages. Molecular modeling exhibited hydrogen bonds played a crucial role for the binding of PhGs with the Nrf2 binding site in Keap1 protein. Conclusions Natural PhGs-induced protection against LPS-induced inflammatory response via activating Keap1/Nrf2/HO-1 signaling pathway in RAW 264.7 macrophages were confirmed, which provided experimental and theoretical basis for the deeper use of C. Kwangtungensis in the treatment and prevention of diseases related to inflammation and oxidative stress.

Forsythiae Fructus (FF) is a widely used folk medicine in China, Japan, and Korea. The distribution of bioactive constituents throughout the fruit segments has rarely been addressed, although mounting evidence suggests that plant secondary metabolites are synthesized and distributed regularly. The phytochemical profiles of three segments of FF (pericarp, stalk and seed) were firstly revealed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based quantitative analysis of twenty-one bioactive constituents, including three phenylethanoid glycosides, five lignans, eight flavonoids, and five phenolic acids to explore the spatial distribution of bioactive constituents. Furthermore, the hierarchical clustering analysis (HCA) and one-way analysis of variance (one-way ANOVA) were conducted to visualize and verify the distribution regularity of twenty-one analytes among three segments. The results showed that phytochemical profiles of the three segments were similar, i.e., phenylethanoid glycosides covering the most part were the predominant compounds, followed by lignans, flavonoids and phenolic acids. Nevertheless, the abundance of twenty-one bioactive constituents among three segments was different. Specifically, phenylethanoid glycosides were highly expressed in the seed, lignans were primarily enriched in the stalk, flavonoids were largely concentrated in the pericarp, while the contents of phenolic acids showed no much difference among various segments. The research improves our understanding of distribution patterns for bioactive constituents in FF, and also complements some scientific data for further exploring the quality formation mechanism of FF.

A new phenylpropanoid (1), a new alkaloid (11), and a new natural polyacetylene (17), together with nine phenolic compounds (2–10), five alkaloids (12–16), three polyacetylenes (18–20), three triterpenoidal saponins (21–23), one phenylethanoid glycoside (24), and three hexyl glycosides (25–27) with previous known structures, were isolated from the roots of Codonopsis lanceolata. All of the isolates 1–27 were evaluated for their inhibitory effects on LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages and cell viability in A2780 human ovarian cancer cells. Among the isolates, lancemasides A and B have a significant inhibitory effect on the production of NO in RAW264.7 cells (IC50 values

Alzheimer’s disease (AD), a neurodegenerative disorder, is characterized by aggregation of amyloid β-protein (Aβ). Aβ aggregates through β-sheet formation and induces cytotoxicity against neuronal cells. Inhibition of Aβ aggregation by naturally occurring compounds is thus a promising strategy for the treatment of AD. We have already reported that caffeoylquinic acids and phenylethanoid glycosides, which possess two or more catechol moieties, strongly inhibited Aβ aggregation. Clovamide (1) containing two catechol moieties, isolated from cacao beans (Theobroma cacao L.), is believed to exhibit preventive effects on Aβ aggregation. To investigate the structure-activity relationship of clovamide (1) for the inhibition of Aβ aggregation, we synthesized 1 and related compounds 2–11 through reaction between l -DOPA, d -DOPA, l -tyrosine, or l -phenylalanine and caffeic acid, p-coumaric acid, or cinnamic acid, and compounds 12 and 13 were derived from 1. Among tested compounds 1–13, those containing one or two catechol moieties exhibited potent anti-aggregation activity, whereas the non-catechol-type related compounds showed little or no activity. This suggests that at least one catechol moiety is essential for inhibition of Aβ42 aggregation, and this activity increases depending on the number of catechol moieties. Consequently, clovamide (1) and its related compounds may be a promising therapeutic option for inhibiting Aβ-mediated pathology in AD.

Ethnopharmacological relevance Forsythiae Fructus (called Lianqiao in Chinese), the fruit of Forsythia suspensa (Thunb.) Vahl, is utilized as a common traditional medicine in China, Japan and Korea. It is traditionally used to treat pyrexia, inflammation, gonorrhea, carbuncle and erysipelas. Depending on the different harvest time, Forsythiae Fructus can be classified into two forms, namely Qingqiao and Laoqiao. The greenish fruits that start to ripen are collected as Qingqiao, while the yellow fruits that are fully ripe are collected as Laoqiao. Both are applied to medical use. This review aims to provide a systematic summary of F. suspensa (Forsythia suspensa (Thunb.) Vahl) and to reveal the correlation between the traditional uses and pharmacological activities so as to offer inspiration for future research. Materials and methods All corresponding information about F. suspensa was searched by Scifinder and obtained from scientific databases including Springer, Science Direct, Wiley, Pubmed and China Knowledge Resource Integrated (CNKI). Local dissertations and books were searched as well. Results According to classical Chinese herbal texts and Chinese Pharmacopoeia, Forsythiae Fructus dominantly displays heat-clearing and detoxifying effects in TCM prescriptions. In modern research, more than 230 compounds were separated and identified from F. suspensa. 211 Of them were isolated from fruits. Lignans and phenylethanoid glycosides are considered as the characteristic and active constituents of this herb, such as forsythiaside, phillyrin, rutin and phillygenin. They exhibited anti-inflammatory, antioxidant, antibacterial, anti-virus, anti-cancer and anti-allergy effects, etc. Currently, there is no report on the toxicity of Forsythiae Fructus, despite slight toxicity of forsythiaside reported in local publications. Compared to Laoqiao, Qingqiao contains higher levels of forsythiaside, forsythoside C, cornoside, rutin, phillyrin, gallic acid and chlorogenic acid and lower levels of rengyol, β-glucose and S-suspensaside methyl ether. Conclusion Heat-clearing actions of Forsythiae Fructus are based on the anti-inflammatory and antioxidant properties of lignans and phenylethanoid glycosides. Detoxifying effects attribute to the antibacterial, antiviral and anti-cancer activities of Forsythiae Fructus. And traditional Chinese medicine (TCM) characteristics of Forsythiae Fructus (bitter flavor, slightly cold nature and lung meridian) supported its strong anti-inflammatory effects. In addition, the remarkable anti-inflammatory and antioxidant capacities of Forsythiae Fructus contribute to its anti-cancer and neuroprotective activities. The higher proportion of lignans and phenylethanoid glycosides in Qingqiao than Laoqiao might explain the better antioxidant ability of Qingqiao and more frequent uses of Qingqiao in TCM prescriptions. For future research, more in vivo experiments and clinical studies are encouraged to further clarify the relation between traditional uses and modern applications. Regarding to Qingqiao and Laoqiao, they remain to be differentiated by all-round quality control methods, and the chemical compositions and clinical effects between them should be compared.

UDP-glycosyltransferases (UGTs) are an important and functionally diverse family of enzymes involved in secondary metabolite biosynthesis. Coumarin is one of the most common skeletons of natural products with candidate pharmacological activities. However, to date, many reported GTs from plants mainly recognized flavonoids as sugar acceptors. Only limited GTs could catalyze the glycosylation of coumarins. In this study, a new UGT was cloned from Cistanche tubulosa, a valuable traditional tonic Chinese herb, which is abundant with diverse glycosides such as phenylethanoid glycosides, lignan glycosides, and iridoid glycosides. Sequence alignment and phylogenetic analysis showed that CtUGT1 is phylogenetically distant from most of the reported flavonoid UGTs and adjacent to phenylpropanoid UGTs. Extensive in vitro enzyme assays found that although CtUGT1 was not involved in the biosynthesis of bioactive glycosides in C. tubulosa, it could catalyze the glucosylation of coumarins umbelliferone 1, esculetine 2, and hymecromone 3 in considerable yield. The glycosylated products were identified by comparison with the reference standards or NMR spectroscopy, and the results indicated that CtUGT1 can regiospecifically catalyze the glucosylation of hydroxyl coumarins at the C7-OH position. The key residues that determined CtUGT1's activity were further discussed based on homology modeling and molecular docking analyses. Combined with site-directed mutagenesis results, it was found that H19 played an irreplaceable role as the crucial catalysis basis. CtUGT1 could be used in the enzymatic preparation of bioactive coumarin glycosides.

Two new iridoid glycosides, scrophularosides A and B (1–2), two phenylethanoid glycosides, scrophularosides C-D (3–4) and eight known compounds (5-12) were isolated from the roots of Scrophularia ningpoensis. Their structures were elucidated via the interpretation of spectroscopic methods, especially 2D NMR and mass analyses. Compound 1 was a novel iridoid glycoside which possessed a 5/6/7/6 ring system with an unprecedented trioxabicyclo [4.3.1] decane core. The anti-inflammatory potential of new compounds 1–4 was evaluated by determining their ability to inhibit lipopolysaccharide (LPS) induced NO production in RAW 264.7 macrophage cells.

Six new phenylethanoid glycosides possessing dioxane moieties, named forsyoxasides A−F ( 1–6 ), together with four known such compounds ( 7–10 ) were isolated from the fruits of Forsythia suspensa . These structures were illustrated by extensive NMR spectroscopic techniques and by comparing their NMR data with the related literatures. Notably, forsyoxaside A ( 1 ) is a novel dioxane phenylethanoid glycoside with an axial aromatic ring, which is rare in the natural sources. Compounds 1 , 4 , 7 and 8 showed remarkable bioactivities against rotenone induced PC12 cell damage. Furthermore, 1 and 7 displayed strong activities against serum deprivation induced damage on the same cells.

Five caffeoyl phenylethanoid glycosides, including two new ones linderruelliosides A (1) and B (2), were isolated from the leaves and stems of Lindernia ruellioides. Their structures were elucidated on the basis of spectroscopic methods, including extensive NMR and MS spectra. In addition, all these compounds were tested for their anti-HBV activity. Compounds 1, 3, and 4 showed anti-HBV activities, with IC50 values of 54.87, 30.74, and 69.02 μM for HBsAg and 26.70, 5.17, and 7.08 μM for HBeAg, respectively.

Introduction Olea europaea L. organs such as leaves, stems and roots have been associated with numerous in vivo and in vitro biological activities and used for traditional medicinal purposes. However, tree wood is an untapped resource with little information about their chemical composition. Objective That is why, the objective of this study is to increase the knowledge about phytochemicals from ‘Chemlali’ olive wood by means of mass spectrometry-based analyses. Its comparison with by-products derived from leaves was also studied. Methodology Hydromethanol extracts from wood and leaves with stems of ‘Chemlali’ olive cultivar were analysed using reversed-phase (RP) high-performance liquid chromatography (HPLC) coupled to two detection systems: diode-array detection (DAD) and quadrupole time-of-flight (QTOF) mass spectrometry (MS) in negative ion mode. Tandem MS experiments were performed to establish the chemical structure of olive phytochemicals. Results A total of 85 compounds were characterised in the studied olive parts and classified as: sugars (3), organic acids (5), one phenolic aldehyde, simple phenolic acids (6), simple phenylethanoids (5), flavonoids (14), coumarins (3), caffeoyl phenylethanoid derivatives (6), iridoids (5), secoiridoids (32), and lignans (5). To our knowledge, the major part of these metabolites was not previously reported in olive tree wood, and 10 olive chemical constituents were identified for the first time in the Oleaceae family. Conclusion The results presented here demonstrated the usefulness of the methodology proposed, based on RP-HPLC-DAD-ESI-QTOF-MS and MS/MS, to develop an exhaustive metabolic profiling and to recover new biologically active compounds in olive wood with pharmacologic and cosmetic potential. Copyright © 2017 John Wiley & Sons, Ltd.

Previous phytochemical investigations of Akebiae Caulis resulted in the isolation of triterpenes, triterpene glycosides, phenylethanoid glycosides and megastigmane glycoside. Amyloid beta (Aβ), the main component of the senile plaques detected in Alzheimer's disease, induces cell death. However, only a limited number of studies have addressed the biological and pharmacological effects of Akebiae Caulis. In particular, the inhibitory activity of Akebiae Caulis against Aβ42 fibrillogenesis remains unclear. Herein, a new triterpene glycoside, akequintoside F (1), along with nine known compounds pulsatilla saponin A (2), collinsonidin (3), akebonic acid (4), hederagenin (5), 1-(3',4'-dihydroxycinnamoyl) cyclopentane-2,3-diol (6), asperosaponin C (7), leontoside A (8), quinatic acid (9), and quinatoside A (10) were isolated from Akebiae Caulis using repeated column chromatography with silica gel, LiChroprep RP-18, and MCI gel. The chemical structures of compounds 1-10 were illustrated based on 1D and 2D NMR spectroscopy, including 1H-1H COSY, HSQC, HMBC and NOESY spectroscopic analyses. Compound 1 a novel compound and known compounds 6 and 7 were isolated for the first time from this plant. Among these compounds, 1, 3, 4, 5 and 7 displayed significant inhibitory effects on Aβ42 induced fibrillogenesis. We present the first report of new compound 1 and the inhibitory effects of components from Akebiae Caulis on Aβ42 fibrillogenesis.

The tea-like beverage Stevia rebaudiana Bertoni (Stevia) is popular in China because it reduces blood glucose and has a sweet taste. In this work, a comprehensive quality assessment of Stevia led to the discovery of five phenylethanoid glycosides, namely steviophethanoside (1), cuchiloside (2), salidroside (3), icariside D (4), and tyrosol (5). Of them, compound 1 is a novel compound. Mass spectrometry and NMR spectroscopy were employed to confirm the absolute configuration. A hydrolytic step with 4 N TFA at 95 &deg, C for 4 h was used to confirm the monosaccharides. In addition, Discovery Studio 4.0 was used to predict the ADME and toxicity activity of compound 1. The results suggested that compound 1 was biocompatible and had poor toxicity, which was verified by rat INS-1 islet &beta, cells through an MTT assay. Meanwhile, a significant stimulatory effect on INS-1 cells was observed, which indicated a hypoglycemic effect of compound 1. This is the first report that describes a natural, novel, and hypoglycemic phenylethanoid glycoside in Stevia.

The Scrophularia genus is a rich source of phenylethanoid glycosides, with diverse biological activities including anti-diabetic properties. This study investigated anti-type 2 diabetic potential and active component of Scrophularia flava Grau. A new phenylethanoid glycoside was isolated from aerial parts of the plant and identified as 2-(4-hydroxy-3-methoxyphenyl) ethyl 6-deoxy-3-O-[(2E)-3-(3 hydroxy-4-methoxyphenyl) prop-2-enoyl]-α-rhamnopyranosyl-(1 → 3)-[α-rhamnopyranosyl-(1 → 6)]-4-O-[(2E)-3-(4-hydroxy-3-methoxyphenyl) prop-2-enoyl]-β-glucopyranoside. It was named flavaioside. The structure of flavaioside was identified based on 1H NMR, 13C NMR, DEPT-HSQC, COSY, HMBC, NOESY and LC-ESI-MS-MS. Total methanol extract, fractions (A-F) and specific main phenylethanoid glycoside (flavaioside), were assessed for inhibitory effects against the α-glucosidase enzyme (in vitro anti-type 2 diabetic assay). The antioxidant activities of methanol extracts, all fractions and isolated flavaioside were identified based on 2, 2′-diphenyl-1-picrylhydrazyl radical (DPPH ) scavenging activity, 2, 2′-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid radical cation (ABTS +) scavenging activity, phosphomolybdenum method, and metal chelating activity. In comparison to the other fractions, the best antioxidant result was observed in fraction E and its main compound, flavaioside, in DPPH (IC50 = 4.26, 2.57 µg/mL) and ABTS + (EC50 = 55.45, 6.34 µg/mL) scavenging activities. Flavaioside showed significantly stronger activities than α-tocopherol and ascorbic acid in DPPH and ABTS + assays. Furthermore, flavaioside showed a potent inhibitory activity on the α-glucosidase enzyme which was comparable with the known anti-type 2 diabetic drug, acarbose (91.85%, and 92.87%, respectively). Fraction E and flavaioside showed α-glucosidase inhibitory activities with IC50 values, 65.05 and 6.50 µg/mL. The plant and its isolated flavaioside can possess acceptable anti-type 2 diabetic potential and anti-oxidant activity.

Acanthus ilicifolius herb (AIH), the dry plant of Acanthus ilicifolius L., has long been used as a folk medicine for treating acute and chronic hepatitis. Phenylethanoid glycosides (PhGs) are one family of the main components in AIH with hepatoprotective, antioxidant, and anti-inflammatory activities. In this study, the pharmacokinetics of AIH was investigated preliminarily by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS). A simultaneously quantitative determination method for four PhGs (acteoside, isoacteoside, martynoside, and crenatoside) in rat plasma was first established by UPLC-MS/MS. These four PhGs were separated with an ACQUITY UPLC BEH C18 column (2.1 &times, 50 mm, 1.7 &mu, m) by gradient elution (mobile phase: MeCN and 0.1% formic acid in water, 0.4 mL/min). The mass spectrometry detection was performed using negative electrospray ionization (ESI&minus, ) in multiple reaction monitoring (MRM) mode. By the established method, the preliminary pharmacokinetics of AIH was elucidated using the kinetic parameters of the four PhGs in rat plasma after intragastric administration of AIH ethanol extract. All four PhGs showed double peaks on concentration-time curves, approximately at 0.5 h and 6 h, respectively. Their elimination half-lives (t1/2) were different, ranging from 3.42 h to 8.99 h, although they shared similar molecular structures. This work may provide a basis for the elucidation of the pharmacokinetic characteristics of bioactive components from AIH.

Duranta erecta L.is a valuable herb used in traditional system of medicine in India and China for the treatment of malaria and abscesses. The presence of phenylethanoid (e.g., acteoside as major bioactive) in addition to iridoid and flavonoids glycosides are mainly responsible for reported pharmacological properties. Although D. erecta is widely used in many Asian countries, the quality assurance of raw herb and its derived products are still in question, due to the lack of validated protocol. Current Indian guidelines for quality assurance of phytopharmaceutical product demands accurate determination of minimum four chemicals. Moreover, there is no chromatographic method to simultaneously analyse acteoside, isoacteoside, durantoside I, quercetin, and methylapigenin-7-O-β-D-glucopyranuronate in D. erecta. The present study establishes a systematic approach for the quality evaluation of D. erecta with efficient and validated UPLC-PDA method that simultaneously analyses the five bioactive marker chemicals in D. erecta . A fast, sensitive, and reliable ultraperformance liquid chromatography-photodiode array (UPLC–PDA) method was developed for the quantification five marker compounds-acteoside, isoacteoside, durantoside-I, quercetin, and methylapigenin-7-O-β-D-glucopyranuronate in D. erecta . The optimized UPLC conditions on Reverse phase column Phenomenex Luna® (C 18 , 2.5 μm, 2.0 × 100 mm)) and binary gradient elution resulted in best separation for all five targeted phytoconstituents. Validation characteristics viz. linearity (r 2 >0.999), accuracy (%RSD −1 ; LOQ- 0.90–1.35 μg mL −1 ) were satisfying the ICH criteria. Uncertainty in the measurement was also estimated using method validation data and other sources to fulfil the technical requirement of ISO 17,025:2017. It is the first validated method that provides the simultaneous and accurate analysis of five bioactive phytoconstituents of D. erecta in short time with defined traceability and accuracy profile. Further, it delivers a holistic quality analysis of raw medicinal herb and its preparation.

Cistanche species, the ginseng of the desert, has been recorded to possess many biological activities in traditional Chinese pharmacopoeia and has been used as an anti-aging medicine. Three phenylethanoid glycosides&mdash, echinacoside, tubuloside A, and acteoside&mdash, were detected in the water extract of Cistanche tubulosa (Schenk) R. Wight and the major constituent, echinacoside, was further purified. Echinacoside of a concentration higher than 10&minus, 6 M displayed significant activity to stimulate growth hormone secretion of rat pituitary cells. Similar to growth hormone-releasing hormone-6, a synthetic analog of ghrelin, the stimulation of growth hormone secretion by echinacoside was inhibited by [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P, an inverse agonist of the ghrelin receptor. Molecular modeling showed that all the three phenylethanoid glycosides adequately interacted with the binding pocket of the ghrelin receptor, and echinacoside displayed a slightly better interaction with the receptor than tubuloside A and acteoside. The results suggest that phenylethanoid glycosides, particularly echinacoside, are active constituents putatively responsible for the anti-aging effects of C. tubulosa and may be considered to develop as non-peptidyl analogues of ghrelin.

Cistanche tubulosa aqueous extract (CTE) is already used as a botanical prescription drug for treating dementia in China. Our previous studies reported that phenylethanoid glycosides of CTE have anti-Alzheimer&rsquo, s disease (AD) activity by inhibiting amyloid &beta, peptide (A&beta, ) aggregation and deposition. However, recent studies considered that the phenylethanoid glycosides may be metabolized by intestinal bacteria, because all analysis results showed that the bioavailability of phenylethanoid glycosides is extremely low. In this study we demonstrate how iron chelation plays a crucial role in the A&beta, aggregation and deposition inhibition mechanism of phenylethanoid glycosides of CTE. In addition, we further proved phenylethanoid glycosides (1&ndash, 3) could reach brain. Active CTE component and action mechanism confirmation will be a great help for product quality control and bioavailability studies in the future. At the same time, we provide a new analysis method useful in determining phenylethanoid glycosides (1&ndash, 3) in plants, foods, blood, and tissues for chemical fingerprint and pharmacokinetic research.

In recent years, the use of Sideritis species as bioactive agents is increasing exponentially. The present study aimed to investigate the chemical constituents, as well as the anti-ageing potential of the cultivated Sideritis euboea Heldr. The chemical fingerprinting of the ethyl acetate residue of this plant was studied using 1D and 2D-NMR spectra. Isomeric compounds belonging to acylated flavone derivatives and phenylethanoid glycosides were detected in the early stage of the experimental process through 2D-NMR techniques. Overall, thirty-three known compounds were isolated and identified. Some of them are reported for the first time not only in S. euboea, but also in genus Sideritis&nbsp, L. The anti-ageing effect of the ethyl acetate residue and the isolated specialized products was assessed as anti-hyaluronidase activity. In silico docking simulation revealed the interactions of the isolated compounds with hyaluronidase. Furthermore, the in vitro study on the inhibition of hyaluronidase unveiled the potent inhibitory properties of ethyl acetate residue and apigenin 7-O-β-d-glucopyranoside. Though, the isomers of apigenin 7-O-p-coumaroyl-glucosides and also the 4′-methyl-hypolaetin 7-O-[6′′′-O-acetyl-β-d-allopyranosyl]-(1→2)-β-d-glucopyranoside exerted moderate hyaluronidase inhibition. This research represents the first study to report on the anti-hyaluronidase activity of Sideritis species, confirming its anti-inflammatory, cytotoxic and anti-ageing effects and its importance as an agent for cosmetic formulations as also anticancer potential.

International audience; Dolichandrone spathacea (L.f.) K. Schum. named “mangrove trumpet tree” is a common smooth tree growing wild in riverbanks and mangroves of the Asia-Pacific area. The leaves of this traditional medicinal plant are used in different countries to treat oral thrush (as mouthwash), flatulence and bronchitis (juice of leaves) [1, 2, 3]. The sole report on the plant found in the literature mentioned the detection of flavonoids, triterpenes and tannins [4].Chemical investigation of the methanolic extract of leaves of a sample collected in Vietnam, furnished 16 iridoids, 3 saponins, 3 phenylethanoid glycosides, 4 flavonoid glycosides, 3 monoterpenic acids, 5 phenolic acids and 1 megastigman glucoside. Their structures were established by spectral means, particularly extensive 2D NMR and MS-MS, and from partial hydrolysis. Among these compounds, five are new.With regard to the traditional use of the leaves against various infections and according to literature results on the antimicrobial activity of the methanolic extract against MRSA [4], we set to study our material along these lines. Thus, the antimicrobial activity of five extracts and of all isolated compounds was evaluated against 22 microorganisms using methods such as bioautography, measurement of MIC (minimum inhibitory concentration) on microplates, and screening using a multiple inoculator (Steers) [5]. At variance with most of the literature, we chose to determine the MIC against a large spectrum of microorganisms in order to discover extracts with a broad-scale activity.The results reveal for the first time the presence in this species of several new natural compounds with an interesting level of antimicrobial activity (the lowest MIC = 31.2 µg/ml). The synergy (activity for mixtures of compounds) and in vivo studies with these compounds may be interesting in the future for a valorization approach.

Cistanches Herba is a famous traditional Chinese medicine that has been in use for treating kidney deficiency, impotence, female infertility, morbid leucorrhea, profuse metrorrhagia, and senile constipation. With the exception of studies available for a few single active ingredients such as echinacoside, acteoside, and poliumoside, comprehensive and systematic studies on in vivo metabolism of Cistanches Herba are lacking despite its widespread clinical application. There is no comparative study yet on the metabolites resulting from the traditional usage of Cistanche deserticola and C. tubulosa water extract - two species that are recorded in Chinese Pharmacopoeia. This further restricts research on the therapeutic effect of Cistanches Herba to a great extent. In this study, a robust and unbiased UPLC-Q-TOF-MS combined pattern recognition analysis (orthogonal partial least squared discriminant analysis, OPLS-DA) was employed to rapidly screen prototype components and metabolites of C. deserticola and C. tubulosa water extract in rat urine, feces, and serum. A total of 71 metabolites from C. deserticola including 25 prototype components and 46 metabolites, and 45 metabolites from C. tubulosa including 18 prototype components and 27 metabolites were tentatively identified. Out of these, 10 metabolites were characterized for the first time in these two species. Results of this study indicate that phenylethanoid glycosides (PhGs) are mainly metabolized into degradation products in the gastrointestinal tract of rats. The chemical components cistanoside B, C, D, and E exist only in C. deserticola and release methylated hydroxytyrosol (HT) following metabolism. This factor contributes to the difference between metabolites of C. deserticola and C. tubulosa water extract in rats and is responsible for the differential therapeutic effect that these two species of Cistanches Herba have on the same diseases.

Two phenylethanoid glycosides previously not observed in Tectona grandis (teak) wood knots were isolated from 30% aqueous isopropanol extract, purified by HPLC and identified as forsytoside B and i...

Verbascoside (1) is a phenylethanoid glycoside that has antileishmanial activity against Leishmania infantum and Leishmania donovani. In this study, we verified the activity of 1 on Leishmania amazonensis and arginase inhibition. Compound 1 showed an EC50 of 19 μM against L. amazonensis promastigotes and is a competitive arginase inhibitor (Ki = 0.7 μM). Docking studies were performed to assess the interaction of 1 with arginase at the molecular level. Arginase is an enzyme of the polyamine biosynthesis pathway that is important to parasite infectivity, and the results of our study suggest that 1 could be useful to develop new approaches for treating leishmaniasis.

Acteoside, the main and representative phenylethanoid glycosides of Herba Cistanches, possesses wide bioactivities but low oral bioavailability. It may serve as the prodrug and be converted into the active forms in gastrointestinal tract, which mainly occurred in intestinal tract composed of intestinal bacteria and intestinal enzyme. Intestinal bacteria, a new drug target, take a significant role on exerting pharmacological effects of drugs by oral administration. In this paper, acteoside was incubated with human or rat intestinal bacteria or rat intestinal enzyme for 36 h to seek metabolites responsible for pharmacodynamics. The samples were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Besides the parent compound, 14 metabolites were detected and identified based on their retention times and fragmentation patterns in their MS spectra including 8 degradation metabolites, 2 isomers in intestinal bacteria and intestinal enzyme samples and 4 parent metabolites only found in intestinal enzymes. The metabolic pathway of acteoside was thus proposed. Identification of these metabolites of acteoside by the intestinal bacteria or intestinal enzyme gave an insight to clarify pharmacological mechanism of traditional Chinese medicines and identify the real active molecules.

Context Some Ajuga L. (Lamiaceae) species are traditionally used for the treatment of malaria, as well as fever, which is a common symptom of many parasitic diseases. Objective In the continuation of our studies on the identification of antiprotozoal secondary metabolites of Turkish Lamiaceae species, we have investigated the aerial parts of Ajuga laxmannii. Materials and methods The aerial parts of A. laxmannii were extracted with MeOH. The H2O subextract was subjected to polyamide, C18-MPLC and SiO2 CCs to yield eight metabolites. The structures of the isolates were elucidated by NMR spectroscopy and MS analyses. The extract, subextracts as well as the isolates were tested for their in vitro antiprotozoal activities against Plasmodium falciparum, Trypanasoma brucei rhodesiense, T. cruzi and Leishmania donovani at concentrations of 90–0.123 µg/mL. Results Two iridoid glycosides harpagide (1) and 8-O-acetylharpagide (2), three o-coumaric acid derivatives cis-melilotoside (3), trans-melilotoside (4) and dihydromelilotoside (5), two phenylethanoid glycosides verbascoside (6) and galactosylmartynoside (7) and a flavone-C-glycoside, isoorientin (8) were isolated. Many compounds showed moderate to good antiparasitic activity, with isoorientin (8) displaying the most significant antimalarial potential (an IC50 value of 9.7 µg/mL). Discussion and conclusion This is the first report on the antiprotozoal evaluation of A. laxmannii extracts and isolates. Furthermore, isoorientin and dihydromelilotoside are being reported for the first time from the genus Ajuga. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

Ethnopharmacological relevance Acanthus ilicifolius L. has been used as a folk medicine in the treatment of acute and chronic hepatitis in China for a long time. Phenylethanoid glycosides are one of main components in A. ilicifolius L. Aim of the study: The aim of present study was to assess the hepatoprotective activities of total phenylethanoid glycosides from A. ilicifolius L. (APhGs) against carbon tetrachloride (CCl4)-induced liver injury in vivo and in vitro. Materials and method The APhGs was separated by resin column chromatography. The purity of total phenylethanoid glycosides was determined by UV–Vis spectrophotometry using acteoside as a standard. The hepatoprotective activities of APhGs against CCl4-induced liver injury were performed on experimental mice and L-02 hepatocytes. Moreover, the antioxidant activities of APhGs were tested in vitro. Results The results showed that pre-administration of APhGs to mice decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum, and improved superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) level in serum and liver tissue induced by CCl4. Specifically, the SOD activities of APhGs-H and APhGs-M treatment groups were stronger than that of silymarin treatment group. The protective activities of APhGs were confirmed by histopathological results. Moreover, immunohistochemical analysis showed that APhGs could remarkably down-regulate the protein expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In vitro experiment, APhGs was observed to increase L-02 hepatocyte viability against CCl4-induced hepatotoxicity. In addition, antioxidation assays revealed that APhGs showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and ferric reducing ability. Conclusion Overall, total phenylethanoid glycosides from A. ilicifolius L. displayed promising hepatoprotective effects. These results offer a support for the medicine uses of A. ilicifolius L.

Scrophularia tenuipes is an Algerian-Tunisian endemic species, which has not been studied yet. Ethyl acetate (EA) and n-butanol (Bu) fractions obtained from Scrophularia tenuipes were investigated for their health benefit properties, in particular with respect to in vivo/in vitro anti-inflammatory and antioxidant activities, as well as their potential to inhibit key enzymes with impact in diabetes (&alpha, glucosidase and &alpha, amylase). The fractions had a distinct phytochemical composition, of which EA was richer in total phenolic compounds (225 mg GAE/g) and mostly composed of the phenylethanoid acetyl martynoside. Compared to EA, Bu had higher amounts of total flavonoids, and according to the result obtained from UHPLC-DAD-ESI-MSn analysis, harpagoside (iridoid) was its major phytochemical. EA fraction was quite promising with regard to the in vivo (at 200 mg/kg, po) anti-inflammatory effect (62% and 52% for carrageenan-induced rat paw edema and xylene-induced ear edema tests, respectively), while Bu fraction exhibited a stronger antioxidant capacity in all tests (IC50 = 68 &micro, g/mL, IC50 = 18 &micro, g/mL and A0.50 = 43 &micro, g/mL for DPPH●, ABTS&bull, +, O2&bull, &minus, scavenging assays and cupric-reducing antioxidant capacity method, respectively). Both fractions also showed a strong effect against &alpha, amylase enzyme (IC50 = 8 &micro, g/mL and 10 &micro, g/mL for EA and Bu fraction, respectively).

Background: Medicinal plant extracts and herbal preparations are complex mixtures of active and ballast substances, which may contain in frequently up to several hundreds of different constituents, with no exactly defined structures at which chromatography undoubtedly is a fundamental tool to overcome the challenges of these phytoanalytics. Aim of the Study: To investigate Pterocephalus frutescens aerial part extracts biologically and chemically and the correlation of biologically active constituents with their corresponding activities. Materials and Methods: Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometer with principal component statistical analysis was used for the identification of phytoconstituents, while spectrophotometer was used for quantitative analysis and both qualitative and quantitative antioxidant effects using stable radical diphenylpicrylhydrazyl, and the cytopathic effect inhibition assay was used for antiviral screening. Results and Conclusion: P. frutescens extracts exhibited antioxidant and antiviral activities along with tentative identifying of 46 compounds from which 38 compounds were correlated with either antiviral and/or antioxidant activities, besides the quantification of phenolic, flavonoid, phenylethanoid, and iridoid contents.

Three phenylethanoid glycosides, echinacoside (1), salidroside (3), and acteoside (6), and three secoiridoid glycosides, isonuezhenide (2), nuezhenoside G13 (4), and specnuezhenide (5), have been extracted and separated by a combined method of ultrahigh pressure extraction (UPE) and high-speed counter-current chromatography (HSCCC) from Ligustri Lucidi Fructus. For the UPE, the optimal extraction was developed with conditions including solvent of 90% ethanol, sample to solvent ratio of 1:20 g/mL, pressure of 200 MPa, and time of 2 min, which rendered the yields of compounds 4 and 5 were 15.0 and 78.0 mg/g, respectively. For the HSCCC separation, the strategy of changing flow rates between 1.0 and 2.0 mL/min allowed the acquisition for 2.7 mg of compound 1, 4.5 mg of compound 2, 6.8 mg of compound 3, 5.9 mg of compound 4, 11.2 mg of compound 5, and 2.2 mg of compound 6 in one separation run under the solvent system of ethyl acetate:n-butanol:water (2:1:3, v/v) from 200 mg of the UPE extract. The structures of these phenylethanoid and secoiridoid glycosides were elucidated by extensive spectroscopic methods.

Chirita drakei Burtt (now accepted as Primulina drakei (B.L. Burtt) Mich. Möller & A. Weber) is growing on limestone mountain slopes of Ha Long Bay islands in Vietnam. The chemical investigation of the aerial parts of C. drakei led to the isolation and structural elucidation of two new compounds named chiridrakoside A (1) and chiridrakoside B (2) besides twelve known compounds comprising five phenylethanoid glycosides (3–7), two lignans (8, 9), a phenyl propanoid (10), an anthraquinone (11), a furan derivative (12) and two triterpenes (13, 14). All described compounds, except 4, 5 and 11, were obtained for the first time from the genera Chirita or Primulina. The cytotoxic activity of the isolated compounds was evaluated against the four human cancer cell lines KB (mouth epidermal carcinoma), HepG2 (hepatocellular carcinoma), Lu (lung carcinoma) and MCF7 (breast carcinoma). Epoxyconiferyl alcohol (10) exhibited cytotoxic activity against the tested cell lines (IC50 from 46 to 128 μM).

Positional isomerization, an inducement leading to instability of phenylethanoid glycosides (PhGs) containing the caffeoyl moiety linked to C-3/4 of the central saccharide, is reported. Magnolosides M, A and F from Magnolia officinalis were found to be transformed into their isomers magnolosides A, D, M and B, respectively, which indicated that PhGs containing the caffeoyl moiety linking to C-3/4 of the central saccharide were unstable, and the caffeoyl group could be transferred to either C-4/3 or C-6 of the central saccharide. In addition, among the factors of temperature, solvent type and exposure time in solvent, temperature was found to play a critical role in initiation of positional isomerization of PhGs. In order to retard this isomerization, the temperature should be lower than 40°C during the final purification stages of PhGs.

Salvia viridis L. is an annual herb used in Mediterranean medicine. The purpose of this study was to determine the polyphenol profile of aqueous (decoction and infusion) and hydroethanolic extracts of aerial parts of field-grown S.viridis and to evaluate their antioxidant activity. The polyphenol profiling was performed via UPLC-DAD/ESI-MS. Additionally, the total polyphenol content in extracts tested were determined by UV-Vis spectrophotometry using the Folin-Ciocalteu assay. The antioxidant effect was evaluated by the FRAP, DPPH, ABTS, O2&bull, &minus, scavenging and TBARS methods. The hydroethanolic extract gave the highest content of total phenolic compounds, followed by the infusion. The UPLC-DAD/ESI-MS analysis of extracts showed a total of 19 phenolic compounds identified as flavonoids (four compounds), phenylethanoids (eight compounds) and phenolic acids (seven compounds). Rosmarinic acid was the predominant phenolic acid, verbascoside was the predominant phenylethanoid, while apigenin glucuronide or methylluteolin glucuronide, depending on the sample, were the predominant flavonoids in the analyzed extracts. The presence of a high polyphenol level indicated a high antioxidant activity of both the infusion and the hydroalcoholic extract. These results indicate that S. viridis is a rich resource of phenolic compounds and can be used in dietary applications with the potential to reduce oxidative stress.

The dried flowers and inflorescences of Buddleja officinalis Maxim are used as traditional medicines in China, and aqueous extracts of the flowers have also been used since ancient times as a yellow rice colorant at local festivals. In this study, HPLC-Q-TOF-MS/MS was used to determine the overall chemical composition of this medicine-food plant. A total of 54 compounds, including 23 flavonoids, 19 phenylethanoid glycosides, 7 alkaloids and 5 other compounds, were detected in the methanol extracts of the herb using this method. Among them, 35 compounds were found firstly in this herb. HPLC fingerprints were also developed, together with a method for the simultaneous quantification of 11 constituents that could be used for quality evaluation of B. officinalis. Fingerprint analysis, using 28 characteristic fingerprint peaks, was used to assess the similarities among 12 samples collected from different geographic areas and showed that the similarity was >0.900. Simultaneous quantification of 11 markers in B. officinalis was then performed to determine consistency of quality. Additionally, the total phenolic content and antioxidant capacity of extracts of the 12 samples of B. officinalis flowers were measured using spectroscopic methods. B. officinalis was found to have good antioxidant capacity and to be a potential natural antioxidant. The highest antioxidant capacity was found in the samples from Guizhou, Sichuan and Guangxi Province. Our results provide valuable information for further understanding and exploiting the herb.

Neuroinflammation is a main factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer disease. Our previous studies indicated that the modified Wuziyanzong Prescription (MWP) can suppress neuroinflammatory responses via nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways. However, the anti-neuroinflammatory components of MWP remain unclear. Herein, a target-directed molecular docking fingerprint (TMDF) strategy, via integrating the chemical profiling and molecular docking approaches, was developed to identify the potential anti-neuroinflammatory components of MWP. First, as many as 120 possible structures, including 49 flavonoids, 28 phenylpropionic acids, 18 amides, 10 carotenoids, eight phenylethanoid glycosides, four lignans, two iridoids, and one triterpenoid were deduced by the source attribution and structural classification-assisted strategy. Then, their geometries were docked against five major targets of the NF-κB and MAPKs signaling cascades, including p38-α, IKKβ, ERK1, ERK2, and TRAF6. The docking results revealed diverse contributions of different components towards the protein targets. Collectively, prenylated flavonoids showed intensive or moderate anti-neuroinflammatory activities, while phenylpropanoids, amides, phenylethanoid glycosides, lignans, and triterpenoids exhibited moderate or weak anti-neuroinflammatory effects. The anti-neuroinflammatory activities of four retrieved prenylated flavonoids were tested by Western blotting assay, and the results mostly agreed with those predicted by the docking method. These gained information demonstrates that the established TMDF strategy could be a rapid and feasible methodology to investigate the potential active components in herbal compound prescriptions.