Neolignan Glycoside Research Articles

Bioactive neolignan, iridoid and flavonoid glycosides from the leaves of Vaccinium bracteatum

Two neolignan glycosides including a new one (1), along with seven iridoid glycosides (3 − 9) and nine flavonoid glycosides (10 − 18), were isolated from the leaves of Vaccinium bracteatum. Their structures were established mainly on the basis of 1D/2D NMR and ESIMS analyses, as well as comparison to known compounds in the literature. The structure of 1 with absolute stereochemistry was also confirmed by chemical degradation and ECD calculation. Selective compounds showed antiradical activity against ABTS and/or DPPH. Moreover, several isolates also suppressed the production of ROS in RAW264.7 cells and exerted neuroprotective effect toward PC12 cells.

Neurotrophic phenolic glycosides from the roots of Armoracia rusticana

Armoracia rusticana P. G. Gaertner. belongs to the Brassicaceae family and has aroused scientific interest for its anti-inflammatory and anticancer activities. In a continuing investigation to discover bioactive constituents from A. rusticana, we isolated 19 phenolic glycosides including three undescribed flavonol glycosides and one undescribed neolignan glycoside from MeOH extract of this plant. Their structures were elucidated based on NMR spectroscopic analysis (1H, 13C, 1H–1H COSY, HSQC, and HMBC), HRESIMS, and chemical methods. The determination of their absolute configuration was accomplished by ECD and LC-MS analysis. All the compounds were assessed for their potential neurotrophic activity through induction of nerve growth factor in C6 glioma cell lines and for their anti-neuroinflammatory activity based on the measurement of inhibition levels of nitric oxide production and pro-inflammatory cytokines (i.e., IL-1β, IL-6, and TNF-α) in lipopolysaccharide-activated microglia BV-2 cells.

Neuroprotective neolignan glycosides from the pseudobulbs of Bletilla striata

Four undescribed neolignan glycosides, bletineosides A–D (1–4) were isolated from the pseudobulbs of Bletilla striata. Their structures with absolute configurations were elucidated on the basis of spectroscopic analyses, along with acidic hydrolysis reactions and ECD experiments. All isolates were evaluated for their neuroprotective activities against glutamate-induced PC12 cell injury. Compound 3 and 4 showed significantly neuroprotective effects at the concentration of 10 μM when compared with the model group. Compounds 1–4 represented the first examples of neolignan glycosides from the genus Bletilla. This study disclosed the potency of Bletilla striata as a new source of anti-neurodegenerative agents.

Four new diastereoisomeric neolignan glycosides from the root bark of Lycium chinense Miller. and their α-glucosidase inhibitory activity

Four new diastereoisomeric neolignan glycosides (1–4) along with nine known lignan glycosides (5–13) were isolated from the root bark of Lycium chinense Mill. Their structures with absolute configurations were elucidated on the basis of NMR spectroscopy, ECD, Mo2(OAc)4-induced ECD spectra, enzymatic hydrolysis and acid hydrolysis. The isolated compounds were evaluated for their α-glucosidase inhibitory activity. Compounds 8 and 13 exhibited moderate inhibitory activities against α-glucosidase with IC50 values of 26.82 ± 2.71 and 43.14 ± 2.81 μg/mL.

Three Neolignan Glycosides from the Root of Nothopanax davidii

Three neolignan glycosides, including a new compound (7S,8R)-dihydro-3'-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1'-benzofuranpropanol-9-O-β-D-xylopyranoside (1), were isolated from the root of Nothopanax davidii. Their structures were determined by extensive spectroscopic analyses, particularly NMR, HR-ESI-MS, and ECD experiments, and the absolute configuration of 2 was first definitively determined. The anti-tumor activity was assessed on four tumor cells by MTT assay, the anti-inflammatory activity was determined by inhibition of NO production in LPS reduced RAW264.7 cells, and the interaction with iNOS was predicted by molecular docking. At the dose of 100 μM, the three neolignan glycosides showed no cytotoxic activity against HepG2, HCT116, HeLa and A549 human tumor cells, but significantly inhibited LPS induced NO generation in RAW264.7 cells with inhibition rates of 31.53 %, 23.95 %, and 20.79 %, respectively, showing weak anti-inflammatory activity, possibly due to their binding to key residues of iNOs involved in inhibitor binding.

Phenolic Glycosides from the Leaves of Iodes cirrhosa Turcz. with Cytotoxic and Antimicrobial Effects.

In the present study, 14 phenolic glycosides, including one new neolignan glycoside, iodescirrhoside A (1), three new flavonol glycosides, iodescirrhosides B-D (2-4), and 10 known metabolites were obtained from the methanol extract of Iodes cirrhosa leaves. Structural elucidation was performed by interpretating the 1D- and 2D- NMR, HR-ESI-MS, and CD spectra in comparison with literature data. All compounds were noncytotoxic to LU-1, HepG2, MCF-7, SK-Mel-2, and LNCaP cancer cell lines. Compound 11 significantly inhibited the growth of E. faecalis. In contrast, weak inhibition was observed for 1-9 and 14 against E. faecalis, for 1, 6-8, and 11 against S. aureus, for 6 and 13 against B. cereus, and 2, 4, and 6-9 against C. albicans.

Procyanidins and Phlobatannins from the Twigs of Rosa multiflora and Their Neuroprotective Activity.

Three new procyanidins (1-3), two new phlobatannins (6 and 7), a new flavan-3,4-diol glycoside (9), and a new neolignan glycoside (10), along with three previously reported compounds (4, 5, and 8) were isolated from the twigs of Rosa multiflora. The chemical structures of the new compounds (1-3, 6, 7, 9, and 10) were characterized by spectroscopic data interpretation, including NMR (1H and 13C NMR, 1H-1H COSY, HSQC, HMBC, and NOESY) and HRESIMS analysis. Experimental ECD data analysis was conducted to assign the absolute configurations of the new compounds (1-3, 6, 7, 9, and 10). The absolute configuration of the sugar moieties was verified through a chiral derivatization method and LC-MS analysis. All the isolated compounds (1-10) were evaluated for their anti-neuroinflammatory activity based on inhibitory effects on nitric oxide production using a lipopolysaccharide-stimulated murine microglia BV-2 cell line and for their neurotrophic effects on nerve growth factor induction in C6 glioma.

Phenolic constituents from twigs of Aleurites fordii and their biological activities.

Three new neolignan glycosides (1–3), a new phenolic glycoside (15), and a new cyanoglycoside (16) were isolated and characterized from the twigs of Aleurites fordii together with 14 known analogues (4–14 and 17–19). The structural elucidation of the new compounds was performed through the analysis of their NMR, HRMS, and ECD spectra and by chemical methods. All isolated compounds were tested for their antineuroinflammatory and neuroprotective activities.

Isolation and characterization of neolignan derivatives with hepatoprotective and neuroprotective activities from the fruits of Citrus medica L. var. Sarcodactylis Swingle

The fruit of Citrus medica L. var. sarcodactylis Swingle is a functional food with rich nutrients and medicinal values because of its content of bioactive compounds. A bioactivity-guided chemical investigation from the fruits of C. medica L. var. sarcodactylis Swingle afforded three new benzodioxane neolignans (1–3), three new phenanthrofuran neolignan glycosides (4–6), two new biphenyl-ketone neolignans (7–8), two new 1′,7′-bilignan neolignans (9–10), as well as fourteen known neolignan derivatives (11–24), which were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. These neolignan derivatives were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, IR spectral data and compared with the data described in the literature. Among them, compounds 1–3 and 12–13 exhibited moderate hepatoprotective activities to improve the survival rates of HepG2 cells from 46.26 ± 1.90% (APAP, 10 mM) to 67.23 ± 4.25%, 62.87 ± 4.43%, 60.06 ± 6.34%, 56.75 ± 2.30%, 58.35 ± 6.14%, respectively. Additionally, compounds 7–8 and 21–22 displayed moderate neuroprotective activities to raise the survival rates of PC12 cells from 55.30 ± 2.25% to 66.94 ± 3.37%, 70.98 ± 5.05%, 64.64 ± 1.93%, and 62.81 ± 4.11% at 10 μM, respectively. The plausible biogenetic pathway and preliminary structure–activity relationship of the selected compounds were scientifically summarized and discussed in this paper.

Chemical constituents from the rhizome of Anemone hupehensis

A phytochemical investigation on the rhizome of Anemone hupehensis resulted in the isolation of thirteen compounds, including six neolignan glycosides (1-6), two phenylpropanoid glycosides (7, 8), a phenolic glycoside (9) and four triterpenoid saponins (10-13). The structures of the isolated compounds were elucidated on the basis of spectroscopic data. This is the first report of neolignan glycoside, phenylpropanoid glycoside, and phenolic glycoside from genus Anemone. This is also the first study to report compounds 1-5 and 7-9 from family Ranunculaceae. All the compounds, except 10 were isolated from A. hupehensis for the first time. The chemotaxonomic significance of the isolated compounds was discussed.

Anti-tyrosinase, anti-cholinesterase and cytotoxic activities of extracts and phytochemicals from the Tunisian Citharexylum spinosum L.: Molecular docking and SAR analysis

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 µg/mL. The highest anticholinesterase activity was presented by the same extract with an IC50 value of 99.97 ± 3.01 µg/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 µg/mL, respectively, against the human cervical cancer cell line (HeLa), and IC50 values of 188.23 ± 3.88 and 197.00 ± 4.25 µg/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 D1-D2, 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 µM. The iridoid glycosides exhibited a significant anticholinesterase activity with IC50 values ranging from 17.19 ± 1.02 to 52.24 ± 2.50 µM. 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 µM. The study of the structure–activity relationship (SAR) has been sufficiently and widely discussed. The natural compounds that exhibited the significant bioactivities were docked.

Discovery of Neolignan Glycosides with Acetylcolinesterase Inhibitory Activity from Huangjinya Green Tea Guided by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry Data and Global Natural Product Social Molecular Networking.

Global Natural Product Social feature-based networking was applied to follow the phytochemicals, including nine flavonoid glycosides, six catechins, and three flavonols in Huangjinya green tea. Further, a new 8-O-4'-type neolignan glycoside, camellignanoside A (1), and 15 known compounds (2-16) were isolated through a variety of column chromatographies, and the structure was elucidated extensively by ultra performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry, 1H and 13C nuclear magnetic resonance, heteronuclear single-quantum correlation, heteronuclear multiple-bond correlation, 1H-1H correlation spectroscopy, rotating frame nuclear Overhauser effect spectroscopy, and Nuclear Overhauser effect spectroscopy, and circular dichroism spectroscopies. Compounds 1 and 2 showed acetylcolinesterase inhibition activity, with IC50 = 0.75 and 0.18 μM, respectively.

Identification of phenolic compounds from a unique citrus species, finger lime (Citrus australasica) and their inhibition of LPS-induced NO-releasing in BV-2 cell line

In this study, a unique citrus species (Citrus australasica) was selected, and its fruit characteristics, phenolic compounds and ability to inhibit inflammation were preliminarily studied. Finger lime fruits showed distinctive features in shape, size, weight, colour, total soluble solids, water-soluble pectin, sugar and acids contents. Combining UPLC-HRMS and UPLC-DAD analysis, 31 phenolics, 1 secoiridoid derivative and 1 neolignan glycoside were preliminarily identified and quantified. The phenolics composition of finger limes showed cultivar and tissue specificity. Antioxidant evaluation showed that extracts from finger lime cultivar of ‘XiangBin’ exhibited better antioxidant capacities than cultivar of ‘LiSiKe’, especially in peel. LPS-induced NO-releasing model was performed in the mouse microglia BV-2 cell line. Results illustrated that finger limes inhibited the NO-releasing and the inflammation-related cytokines including IL-1β, IL-6 and TNFα elevation. QRT-PCR revealed that finger lime extracts alleviated LPS-induced upregulation of iNOS, IL-6, JAK2, TNFα, TLR2, TLR4, IL-1β, NF-κB and LPS-induced downregulation of IκBα. This study may expand our knowledge on the physiochemical characteristics and bioactive properties of citrus fruits.

A new neolignan glycoside from Dolomiaea souliei

One new neolignan glycoside, dolomiside A (1), together with 11 known phenylpropanoid glycosides were isolated from Dolomiaea souliei (Franch.) Shih. The structures of these isolates were determined by UV, CD, HR-ESI-TOFMS, 1D and 2D NMR analysis.

High-performance countercurrent chromatographic isolation of acylated iridoid diglycosides from Verbascum ovalifolium Donn ex Sims and evaluation of their inhibitory potential on IL-8 and TNF-α production

In traditional folk medicine, Verbascum species have been used since ancient times to treat respiratory disorders, hemorrhoids, diarrhea, wounds, eczema and other types of inflammatory skin conditions. Despite the fact that more than 200 bioactive constituents (phenylethanoids, flavonoids, neolignan glycosides, phenolic acids, iridoids, saponins and polysaccharides) have been previously isolated from various Verbascum species, to date preparative high-performance countercurrent chromatography (HPCCC) has never been employed for this purpose. Therefore, in this study, simple HPCCC methods were successfully developed with the aim to primarily isolate acylated iridoid diglycosides from Verbascum ovalifolium Donn ex Sims (oval-leaved mullein). By the use of several biphasic solvent systems containing n-hexane, ethyl acetate, n-butanol/methanol and water, premnacorymboside B (3, 4 mg, 95.4% purity), saccatoside (4, 6 mg, 95.7% purity), premnacorymboside A (7, 6 mg, 98.3%), scorodioside (8, 11 mg, 96.0%) and 6-O-(3′',4′'-di-O-trans-cinnamoyl)-α-L-rhamnopyranosylcatalpol (9, 8 mg, 95.3%) were afforded; compounds 7, 8 and 9 have not been previously reported in Verbascum genus. Additionally, two phenolic acids (1, 2), two flavonoids (6, 10) and verbascoside (5) were secondarily isolated. Evaluation of interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α) inhibitory properties of the acylated iridoid diglycosides proved that these compounds down-regulated TNF-α release more efficiently than IL-8 secretion. The activity might be dependent on the degree of esterification, as diacyl derivatives showed more potent effects than monoesters. The HPCCC methods herein developed could serve to large scale isolation of constituents from Verbascum genus for extensive biological investigations.

Chemical constituents, Antibacterial and Acetylcholine esterase inhibitory activity of Cupressus macrocarpa leaves

The chemical constituents of Cupressus macrocarpa were investigated. A new neolignan glycoside (1) in addition to nine known compounds were isolated. The acetylcholinesterase (AChE) inhibitory activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) of different fractions and isolates of C. macrocarpa were evaluated. The light petroleum fraction showed the highest activity in both assays with IC50 value of 88.79 µg/ml and 152.58 µg/ml for the AChE inhibitory activity and MRSA antibacterial activities, respectively. Weak to moderate activity were detected for the isolated compounds.

Three new 2,4′-epoxy-8,5′/8,3′-neolignans from Penthorum chinense

Three new neolignans (1−3), including one 2,4′-epoxy-8,5′-neolignan and two 2,4′-epoxy-8,3′-neolignan glycosides, were isolated from the EtOAc-soluble portion of the water decoction of Penthorum chinense Pursh. Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and electronic circular dichroism (ECD) calculations. Notably, the unusual 2,4′-epoxy-8,3′-neolignan glycosides are reported for the first time.

Neolignan Constituents with Potential Beneficial Effects in Prevention of Type 2 Diabetes from Viburnum fordiae Hance Fruits.

Nine new neolignan glycosides (1-9), viburfordosides A-I, two new neolignans, fordianes A and B (10, 11), and seven known analogues (12-18) have been isolated and identified from the fruits of Viburnum fordiae Hance. The structures and absolute configurations of undescribed neolignan constituents were identified by chemical methods and spectroscopic analyses. The α-glucosidase inhibitory, ABTS•+ and DPPH• scavenging, and anti-inflammatory activities of these secondary metabolites were evaluated. Some of them exhibited significant potency in inhibiting α-glucosidase and scavenging free radicals. Among the 14 metabolites that were found to have the capacity to inhibit NO production in LPS-stimulated RAW264.7 macrophage cells, compounds 2, 4, 6, 10, 11, 14, 17, and 18 were potent with IC50 values of 10.88-41.10 μM. These results support that V. fordiae fruits possessing the neolignan compounds may serve as both a functional food and a medicinal resource to prevent and treat type 2 diabetes (T2D).

Chemical constituents from the branches of Alangium barbatum and their anti-inflammatory activities

Two new sesquiterpenes (1 and 2), one new alkaloid (4), one new neolignan glycoside (14), together with 19 known compounds were isolated from the branches of Alangium barbatum. Their structures were established by spectroscopic analysis. The absolute configuration of 21 was determined for the first time by single-crystal X-ray diffraction analysis with Cu-Kα irradiation. Some of isolates were evaluated for their inhibitory effects on NO production in LPS-induced RAW264.7 macrophages. Compounds 1, 3 and 9 at 10 μM concentrations exhibited mild inhibitory effects on NO production in the range of 25.0 to 32.4. Moreover, these compounds at 25 μM concentration were also found to mildly suppress NF-κB activation in TNF-α induced expression of NF-κB-Luc in Hela cells with inhibition percent in the range of 15.0 to 25.0%.

Isolation of neolignan and phenolic glycosides from the branches of Viburnum macrocephalum f. keteleeri and their α-glucosidase inhibitory activity

Abstract Viburnum macrocephalum f. keteleeri, not well explored in the pharmaceutical field, is a tall deciduous shrub and commonly used as folk medicines for the treatment of type 2 diabetes (T2D). In this study, the dried branches of V. macrocephalum f. keteleeri were extracted with 95% ethanol and the extract was fractionated on the basis of polarity with ethyl acetate and n-butanol. Among the different fractions, the ethyl acetate fraction exhibited the highest α-glucosidase inhibitory activity, and its bioassay-guided fractionation led to the isolation and identification of six compounds including a new 8-O-4′-neolignan glycoside (1), categorized as a rare 7-deoxy skeleton, three previously undescribed phenolic glycosides (2–4), together with two known secondary metabolites (5, 6), which were found for the first time in Viburnum. Noticeably, compound 1 had almost the same intestinal α-glucosidase inhibitory activity as the positive control acarbose.