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Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans (1 – 4) and 12 known lignans (5 – 16) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1 – 16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1 – 16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2 , 6 – 8 and 13 – 16 demonstrate better COX-2 inhibitory effects with IC 50 values from 0.75 to 8.17 μ Μ. These findings provide useful information for the search for natural selective COX-2 inhibitors. [Display omitted] • 16 lignans have been isolated from the extract of Acanthopanacis cortex. • For the first time, lignans 1 – 16 were obtained in this plant. • Compounds 2 , 6 – 8 and 13 – 16 exhibited significant inhibitory effects on cyclooxygenase-2 (COX-2) with high selectivities. [ABSTRACT FROM AUTHOR]

Anemone vitifolia is a small herb found in Asia that is used to treat a range of diseases in Chinese traditional medicine. GNPS-based molecular networking of an Anemone vitifolia specimen revealed the presence of a network containing numerous ions indicating the presence of lignans, several of which suggested that there might be previously undescribed compounds in the extract. Fractionation of the organic extract yielded five undescribed lignans, the vitifolignans, together with one known. The structures were identified based on extensive spectroscopic data analysis (NMR, HR-ESI-MS, and UV), coupling constant calculation and comparison with reported data. Their absolute configurations were determined by comparison of experimental ECD spectra with calculated spectra. Compounds 4/5 showed weak inhibition of LPS-induced NO production in mouse mononuclear macrophages. Molecular Networking aided in the isolation of the vitifolignans, previously undescribed lignans with unusual C-9 side chains; computational methods were crucial in determining their absolute configurations. [Display omitted] • Molecular networking was applied to lignan discovery in Anemone vitifolia. • 3,4-Dibenzyltetrahydrofuran lignans with furanone & glycerol sidechains isolated. • Computation of ECD spectra and semi-synthesis determined absolute configuration. [ABSTRACT FROM AUTHOR]

Five undescribed lignans (1-5), along with sixteen known lignans (6-21), were isolated from the roots of Anthriscus sylvestris using small molecule accurate recognition technology (SMART). The structures of the isolated compounds were determined by comprehensive spectroscopic analyses, and the absolute configurations of compounds 3-5 were elucidated by comparison of their calculated and experimental ECD spectra. Compounds 5, 14-15, 19, and 21 exhibited significantly inhibitory effects against hypoxia-stimulated abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs). Moreover, compounds 5, 14-15, 19, and 21 can significantly restore expression of expression of PASMCs proliferation-related protein, including α-SMA, PCNA, P27, and CyclinD3, which are closely related to cell proliferation., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024. Published by Elsevier Ltd.)

Honokiol (HK) and magnolol (MAG) are typical representatives of neolignans possessing a wide range of biological activities and are employed as traditional medicines in Asia. In the past few decades, HK and MAG have been proven to be promising chemical scaffolds for the development of novel neolignan drugs. This review focuses on recent advances in the medicinal chemistry of HK and MAG derivatives, especially their structure-activity relationships. In addition, it also presents a comprehensive summary of the pharmacology, biosynthetic pathways, and metabolic characteristics of HK and MAG. This review can provide pharmaceutical chemists deeper insights into medicinal research on HK and MAG, and a reference for the rational design of HK and MAG derivatives. This review presents a comprehensive summarization of the pharmacology, biosynthetic pathways, metabolic characteristics, and chemical structure modification of honokiol and magnolol, especially focusing on the derivatives' structure-activity relationships. [Display omitted] • Honokiol and magnolol possess a broad range of biological activities. • This review mainly summarized structure–activity relationships of their derivatives. • It also involves the pharmacology, biosynthetic pathways and metabolites of honokiol. • It provides some ideas for further research on honokiol and magnolol derivatives. [ABSTRACT FROM AUTHOR]

Schisandra lignans are the main bioactive compounds found in Schisandra chinensis fruits, such as schisandrol lignans and schisandrin lignans, which play important roles in organ protection or other clinical roles. Pinoresinol-lariciresinol reductase (PLR) plays a pivotal role in plant lignan biosynthesis, however, limited research has been conducted on S. chinensis PLR to date. This study identified five genes as Sc PLR, successfully cloned their coding sequences, and elucidated their catalytic capabilities. Sc PLR3-5 could recognize both pinoresinol and lariciresinol as substrates, and convert them into lariciresinol and secoisolariciresinol, respectively, while Sc PLR2 exclusively catalyzed the conversion of (+)-pinoresinol into (+)-lariciresinol. Transcript-metabolite correlation analysis indicated that Sc PLR2 exhibited unique properties that differed from the other members. Molecular docking and site-directed mutagenesis revealed that Phe271 and Leu40 in the substrate binding motif were crucial for the catalytic activity of Sc PLR2. This study serves as a foundation for understanding the essential enzymes involved in schisandra lignan biosynthesis. [Display omitted] • Identified five ScPLRs in S. chinensis and cloned their sequence. • Sc PLR3∼5 could recognize both pinoresinol and lariciresinol as substrates. • Sc PLR2 exclusively catalyzed the conversion of (+)-pinoresinol into (+)-lariciresinol. • Identified Phe271 was one of the key sites for the stereoselectivity of Sc PLR2. [ABSTRACT FROM AUTHOR]

Under the guidance of antioxidant evaluation combined with molecular networking, six pairs of enantiomeric lignans including seven undescribed ones (1a , 2a / 2b − 4a / 4b), along with five known analogs (1b , 5a / 5b − 6a / 6b) were isolated from Cimicifuga heracleifolia Kom. Their structures were determined by extensive spectroscopic data analysis, including HRESIMS, 1D and 2D NMR, experimental and calculated ECD. All the enantiomeric isolates were evaluated for antioxidation by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging tests. Compounds 1a and 3a / 3b exhibited great DPPH and ABTS scavenging activities. The results are of great value for understanding structurally interesting enantiomeric lignans with antioxidant activity from C. heracleifolia in depth and providing its further development in functional evaluation and drug development. [Display omitted] • Bioactivity- and GNPS-guided, lignans of Cimicifuga heracleifolia Kom. were isolated. • Six pairs of racemic lignans were obtained and resolved into their enantiomers. • 7 undescribed lignans and 5 known ones were determined by spectroscopic and ECD data. • Compounds 1a and 3a/3b exhibited strong DPPH and ABTS scavenging activities. [ABSTRACT FROM AUTHOR]

In the current study, twenty-two stereochemical 9,9′-epoxylignans including 19 undescribed ones were isolated from the ethanol extract of Syringa pinnatifolia in our continuing effort to understand the overall chemical spectrum of this species. These isolates were structurally elucidated by extensive spectroscopic data analysis, X-ray diffraction, modified Mosher's method, and quantum chemical calculations. Meanwhile, the utilization of 13C NMR calculation and the MAE ΔΔ δ parameter facilitated the stereochemical assignment of groups of lignan stereoisomers. The 13C NMR data were corrected by the averaged errors at each corresponding carbon position in groups of lignan stereoisomers, which improved the theoretic 13C NMR calculation. The finding of the stereochemical structures of 9,9′-epoxylignans is significant. It is helpful to determine the absolute configurations of molecules with the similar core. In addition, these lignans exhibited potential cardioprotective activities on H9c2 cardiomyocytes in vitro and presented significant antioxidant effect. Nineteen undescribed 9,9′-epoxylignans and three known ones were isolated from the stems of Syringa pinnatifolia. The utilization of 13C NMR calculation and the MAE ΔΔ δ parameter facilitated their stereochemical assignments. [Display omitted] • 21 lignans including 19 undescribed ones were isolated from Syringa pinnatifolia. • Stereochemistry was assigned by NMR calculations with MAE ΔΔδ parameter. • Systematical errors were eliminated by the averaged errors. • These lignans exhibited cadioprotective and antioxidant effects. [ABSTRACT FROM AUTHOR]

Four pairs of neolignan enantiomers (±)- 1 − (±)- 4 with a distinctive isochroman moiety, including seven undescribed compounds, were isolated and identified from the fruits of Crataegus pinnatifida. Structural characterization of these compounds was established through comprehensive spectroscopic analyses, as well as quantum chemical calculations of ECD and NMR data. The preliminary bioassay displayed that compounds (+) -2 and (±) -3 exerted protective activities against H 2 O 2 -induced human neuroblastoma SH-SY5Y cells compared with the positive control. These bioactive compounds could be potential candidates for further pharmaceutical applications. Four pairs of neolignan enantiomers with a distinctive isochroman moiety, including seven undescribed compounds (±)- 1 − (±)- 3 and (−)- 4 , were isolated from Crataegus pinnatifida. Some of them exerted potential protective activities against H 2 O 2 -induced SH-SY5Y cells. [Display omitted] • Four pairs of neolignan enantiomers were isolated from Crataegus pinnatifida. • All isolates were separated by chiral resolution. • All isolates possess a distinctive isochroman unit. • (+) -2 and (±) -3 exerted protective activity against H 2 O 2 -induced SH-SY5Y cells. [ABSTRACT FROM AUTHOR]

Ten lignans, including six previously undescribed phenolic ester glycosyl lignans (1 – 6), were isolated from a well-known traditional Chinese medicine, Qin-Jiao, which is the dry root of Gentiana macrophylla Pall. (Gentianaceae). Their structures were determined by spectroscopic and chemical methods, especially 2D NMR techniques. Quantum chemical calculations of theoretical ECD spectra allowed the determination of their absolute configurations. Refer to its traditional applications for the treatment of rheumatic arthralgia and hepatopathy, these compounds were evaluated on a TNF-α induced MH7A human synoviocyte inflammation model and a D-GalN induced AML12 hepatocyte injury model. Compounds 1 , 2 , 5 , and 6 significantly reduced the release of proinflammatory cytokine IL-1β in MH7A cells at 15 μM and they also could strongly protect AML12 cells against D-GalN injury at 30 μM. Flow cytometry and Western blot analysis showed that compound 5 ameliorated D-GalN induced AML12 cell apoptosis by upregulating the expression of anti-apoptotic Bcl-2 protein and down-regulating the expression of pro-apoptotic Bax protein. Six undescribed phenolic ester glycosyl lignans were discovered from the well-known traditional Chinese medicine Gentiana macrophylla. Compound 5 ameliorates D-GalN induced AML12 cell apoptosis by up-regulating Bcl-2 and down-regulating Bax proteins. [Display omitted] • Six undescribed glycosyl lignans were discovered from Gentiana macrophylla. • The absolute configurations were determined by quantum chemical calculations. • Some lignans exhibited promising anti-arthritis and hepatoprotection activities. • Compound 5 ameliorates AML12 cell apoptosis by regulating Bcl-2 and Bax protein expression. [ABSTRACT FROM AUTHOR]

Eleven previously undescribed lignan constituents, including five 8- O -4′ type neolignans, viburnurcosides A–E (1 – 5), three benzofuran type neolignans, viburnurcosides F–H (6 – 8), and three tetrahydrofuran type lignans, viburnurcosides I–K (9 – 11), were isolated from the fruits of Viburnum urceolatum. The structures of all isolates were elucidated by an extensive analysis of the NMR and HRESIMS data. The absolute configurations of these compounds were determined by quantum-chemical electronic circular dichroism calculation and comparison. The sugar units of viburnurcosides A–K were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of monosaccharides. The in vitro enzyme inhibition assay exhibited that viburnurcoside J (10) had the most potent inhibitory activity against α -amylase and α -glucosidase with the IC 50 values of 19.75 and 9.14 μM, respectively, which were stronger than those of the positive control acarbose (37.31 and 26.75 μM, respectively). The potential binding modes of viburnurcoside J (10) with α -amylase and α -glucosidase were also analyzed by molecular modeling. Eleven previously undescribed lignans were characterized from the fruits of Viburnum urceolatum and evaluated for their α -amylase and α -glucosidase inhibitory activities in vitro and in silico. [Display omitted] • Eleven previously undescribed lignans were isolated from V. urceolatum fruits. • The absolute configurations were determined by calculated ECD or CD spectra. • Viburnurcoside J showed potent inhibition against α -amylase and α -glucosidase. • The binding modes of viburnurcoside J with two enzymes were simulated. [ABSTRACT FROM AUTHOR]

A phytochemical study on the fruits of Rubus idaeus L. (Rosaceae) yielded eight pairs of enantiomeric lignans, including one undescribed furolactone named (−)-idaeusinol A and six undescribed furofuran derivatives named (+/−)-idaeusinol B–D. The structures of these isolated compounds were elucidated by spectroscopic analyses and a combination of computational techniques including gauge-independent atomic orbital (GIAO) calculation of 1D NMR data and TD-DFT calculation of electronic circular dichroism (ECD) spectra. Bioactivity screenings suggested that (+)-idaeusinol D exhibited the most significant protective effect against H 2 O 2 -induced neurotoxicity at the concentration of 25 μ M. In contrast, (−)-idaeusinol D, as the enantiomer of (+)-idaeusinol D, showed no effect against H 2 O 2 -induced neurotoxicity at both 25 and 50 μ M concentration. Eight pairs of enantiomeric lignans, including one undescribed furolactone and six undescribed furofuran derivatives were isolated from the fruit of Rubus idaeus. (+)-Idaeusinol D showed obvious neuroprotective activity at 25 μ M concentration. Image 1 • Eight pairs of enantiomeric lignans were isolated from the fruit of red raspberry. • Calculated ECD and NMR were used to confirm their stereostructure. • Their neuroprotective activity against H 2 O 2 -treated SH-SY5Y cell were tested. • (+/−)-Idaeusinol D exhibited enantioselective neuroprotective effects. [ABSTRACT FROM AUTHOR]

A bioassay-guided chemical investigation on the ethyl acetate extract of the stems of Herpetospermum pedunculosum led to the isolation and identification of 22 lignans including 6 previously undescribed ones, herpetosiols A-F. Their structures including stereochemistries were elucidated by analysis of NMR, HRMS and ECD data. The in vitro cytotoxic activities of all isolates were studied against human gastric carcinoma SGC7901, lung carcinoma A549, breast carcinoma MDA-MB-231 and hepatocellular carcinoma HepG2 cell lines. Among them, eight lignans exhibited anti-proliferative effects against four tumor cell lines with IC 50 ranging from 1.7 ± 0.1 to 32.6 ± 1.1 μM. Hedyotol-B displayed potent inhibitory effect with IC 50 values of 1.7 ± 0.1 μM against SGC7901 and 6.1 ± 0.5 μM against A549, respectively. Image 1 • Six undescribed lignans were obtained from Herpetospermum pedunculosum. • The stereochemistry was elucidated by ECD and 2D-NMR. • Eight compounds selectively inhibited the proliferation of four cancer cell lines. [ABSTRACT FROM AUTHOR]

Neocinnamomum delavayi (Lauraceae) leaves with abundant oil cells are seldom attacked by insects, but their chemical constituent and biological function remain obscure. Three furofuran lignans, including (+)-eudesmin (3), (+)-magnolin (4), and demethoxyaschantin (5), were identified to be the major specialized metabolites in the oil cells of N. delavayi leaves through laser microdissection coupled with NMR analysis. Compounds 3 and 4 exhibited obvious antifeedant activity against a generalist insect Spodoptera exigua , and their natural contents in the leaves could effectively defend against generalist insects. Intriguingly, three specific metabolites 9 – 11 , the O -demethylation derivates of compounds 3 – 5 , were identified from a native specialist insect Dindica polyphaenaria feeding with N. delavayi leaves, implying an adaptation mechanism of specialist insects to plant defensive compounds. The results revealed a chemical connection between plants and insects, which would contribute to our understanding of plant-insect interaction and insect management. [Display omitted] • Furofuran lignans were specifically stored in oil cells of Neocinnamomum delavayi by an LMD-NMR-HPLC method. • Furofuran lignans in plant oil cells could play a role in defending generalist insects. • Defensive furofuran lignans were metabolized by the specialist insect to the O -demethylation products. [ABSTRACT FROM AUTHOR]

Nine pairs of undescribed enantiomers, (±)-styraxoids A−I (1 – 9), were isolated from the resin of Styrax tonkinensis , and their structures were assigned by spectroscopic and computational methods. Compounds (±)- 1 are a pair of degraded lignans, and the remaining compounds (±)-(2 – 9) are phenylpropanoid skeletons. Compounds (±)- 8 and (±)- 9 feature a 1,3-dioxolane moiety. The biological evaluation showed that both enantiomers of 1 could inhibit LPS-induced INOS and COX-2 in RAW264.7 cells in a dose-dependent manner. Nine pairs of undescribed enantiomers, (±)-styraxoids A−I (1–9), were isolated from the resin of Styrax tonkinensis (Pierre) Craib ex Hart, and the biological evaluation showed that both enantiomers of 1 could inhibit LPS-induced INOS and COX-2 in RAW264.7 cells in a dose-dependent manner. [Display omitted] • Nine pairs of undescribed enantiomers, (±)-styraxoids A−I (1 – 9), were isolated from the resin of Styrax tonkinensis (Pierre) Craib ex Hart. • Characterization of all new metabolites by using spectroscopic and quantum chemical calculations. • The enantiomers of 1 could inhibited the expressions of iNOS dose-dependently. [ABSTRACT FROM AUTHOR]

Research on natural inhibitors of microglial overactivation derived from members of the Wikstroemia genus revealed that the extract of W. lichiangensis W. W. Sm. Has a remarkable inhibitory effect on nitric oxide production in overactivated microglia. In the present study, thirty-four compounds, including five undescribed sesquiterpenoids [wiksdauctins A–B (1 – 2) and wikscarotins A–C (3 – 5)] and one undescribed lignan [wikstroeminasin A (8)], were isolated from a 95% EtOH extract of W. lichiangensis roots using bio-guided phytochemical research. The structures of the isolated compounds were elucidated using comprehensive spectroscopic analyses. Furthermore, their anti-neuroinflammatory effects were evaluated in lipopolysaccharide-stimulated BV-2 microglia. Seventeen isolated compounds exhibited stronger inhibitory effects than positive control minocycline (IC 50 values of 67.08 ± 1.95 μM), with IC 50 values ranging from 7.35 ± 2.51 to 64.49 ± 3.38 μM. The findings of this study imply that the isolated compounds might serve as potential therapeutic agents for neurodegenerative diseases. Six undescribed and twenty-eight known compounds were characterized from the roots of W. lichiangensis, which had the inhibitory effects on NO production in LPS induced BV-2 microglia. [Display omitted] • Six undescribed compounds were identified from Wikstroemia lichiangensis. • All compounds were evaluated for NO inhibitory effects in LPS-induced BV-2 cells. • Inhibitory effects of seventeen compounds were reported. [ABSTRACT FROM AUTHOR]

Five undescribed lignans, three undescribed phenylethanoid glycosides and eight known compounds were isolated from the root of Isodon ternifolius (D.Don) Kudô (Lamiaceae). The structures of all of the isolated constituents were characterized by physical data analyses including NMR, MS and ECD. The anti-inflammatory activities of the isolates were evaluated based on their ability to inhibit NO, PGE2 and TNF- α production in LPS-induced RAW 264.7 macrophage cells. Six phenyl-naphthalene lignans, ternifoliuslignan A, ternifoliuslignan B, ternifoliuslignan C, ternifoliuslignan D, ternifoliuslignan E and 3-carboxy-6,7-dihydroxy-1-(3′,4′-dihydroxyphenyl) -naphthalene, can substantially inhibit the release of NO with IC 50 values in the range of 9.98–29.14 μM, which are better than the positive reference. These phenyl-naphthalene lignans could markedly decrease the secretions of PGE2 and TNF- α in LPS-induced RAW264.7 cells. Ternifoliuslignan C and ternifoliuslignan D decreased iNOS, COX-2 and NF- κ B/p65 protein expression. A preliminary structure-activity relationship among the phenyl-naphthalene lignans for the anti-inflammatory activity was discussed. [ABSTRACT FROM AUTHOR]

EtOAc extract from the leaves of Terminalia citrina collected in Bangladesh were separated, and seven previously undescribed α-keto tetrahydrofuran lignan glucosides (terminalosides Q to W) were isolated and characterized. NOESY analysis of 1 H NMR spectra and ECD spectroscopic data analysis revealed the absolute stereochemistry of the tetrahydrofuran ring of the isolated constituents as being a (7 S ,8 R ,8′ S )- configuration in terminalosides Q to U and a (7 R ,8 R ,8′ S )- configuration in terminalosides V and W. All of the isolated compounds were evaluated for their estrogenic and anti-estrogenic properties using two types of estrogen-responsive human breast cancer cell lines (MCF-7 and T47D). Terminaloside R, which has a dioxymethylene group in its aromatic ring, inhibited 90% of estradiol-enhanced cell proliferation in T47D and MCF-7 cells at concentrations of 0.01 μM and 0.1 μM, respectively. On the other hand, terminaloside T, the analogous compound which has two oxymethyl groups in place of dioxymethylene, suppressed 90% of cell proliferation selectively in T47D cells at a concentration of 0.01 μM. However, terminaloside W, the 7 R -stereoisomer of terminaloside R, only showed moderate activity. [ABSTRACT FROM AUTHOR]

Bioactivity-guided fractionation of the fruits of Schisandra chinensis , using the proprotein convertase subtilisin-kexin type 9 (PCSK9) mRNA expression screening assay, led to isolation of two previously unknown lignans, 14-tigloylschinlignan D and rel- (7 R, 8 R , 7′ R , 8′ R )-manglisin E, along with 28 known compounds. All structures were established by NMR spectroscopic data as well as CD and MS analysis. All isolates were tested for their inhibitory activities on the mRNA expression of PCSK9. Of the tested compounds, four of the compounds rel- (7 R , 8 R , 7′ R , 8′ R )-manglisin E, (−) - schisandrin C, schinlignan D, and (+)-schisandrol B potently inhibited PCSK9 mRNA expression with IC 50 values of 3.15, 3.85, 0.36, and 1.10 μM, respectively. Furthermore, schinlignan D and (+)-schisandrol B were found to suppress PCSK9 protein expressions and schinlignan D deemed to increase low density lipoprotein receptor expression. [ABSTRACT FROM AUTHOR]

The phytochemical profile of Macropiper excelsum (G.Forst.) Miq. subsp. excelsum (Piperaceae), a shrub which is widespread in New Zealand, was investigated by LC-MS-guided isolation and characterization via HR-ESI-TOF-MS and NMR spectroscopy. The isolated compounds were sensorily evaluated to identify their contribution to the overall taste of the crude extract with sweet, bitter, herbal and trigeminal impressions. Besides the known non-volatile Macropiper compounds, the lignans (+)-diayangambin and (+)-excelsin, four further excelsin isomers, (+)-diasesartemin, (+)-sesartemin, (+)-episesartemin A and B were newly characterized. Moreover, piperine and a number of piperine analogues as well as trans -pellitorine and two homologues, kalecide and (2 E ,4 E )-tetradecadienoic acid N -isobutyl amide were identified in M. excelsum , some of them for the first time. Methyl(2 E ,4 E )-7-(1,3-benzodioxol-5-yl)hepta-2,4-dienoate was identified and characterized for the first time in nature. Sensory analysis of the pure amides indicated that they contributed to the known chemesthetic effects of Macropiper leaves and fruits. Since the pungent piperine has been shown to affect glucose and fatty acid metabolism in vivo in previous studies, piperine itself and four of the isolated compounds, piperdardine, chingchengenamide A, dihydropiperlonguminine, and methyl(2E,4E)-7-(1,3-benzodioxol-5-yl)hepta-2,4-dienoate, were investigated regarding their effects on glucose and fatty acid uptake by enterocyte-like Caco-2 cells, in concentrations ranging from 0.1 to 100 μM. Piperdardine showed the most pronounced effect, with glucose uptake increased by 83 ± 18% at 100 μM compared to non-treated control cells. An amide group seems to be advantageous for glucose uptake stimulation, but not necessarily for fatty acid uptake-stimulating effects of piperine-related compounds. [ABSTRACT FROM AUTHOR]

Nine tetrahydrofuran lignans, including three undescribed spiro-lignans, were isolated from Isatis indigotica Fortune (Brassicaceae). Extensive spectroscopic analyses achieved the structure elucidation of these tetrahydrofuran lignans, and quantum chemical calculation combined with the MAE ΔΔ δ parameter. Notably, isatispironeols A-B have a unique spiro[dienone-tetrahydrofuran] molecular core. These spiro[dienone-tetrahydrofuran] lignans showed comparable neuroprotective effects as the positive control in the H 2 O 2 -induced SH-SY5Y cells model. In addition, (−)-(7 R, 8 S, 1 ′R, 7 ′R, 8 ′R)-isatispironeol A possessed more significant AChE inhibitory activity, further interact sites were also predicted by the in silico assay. Nine tetrahydrofuran lignans, including three undescribed spiro-lignans, were isolated from Isatis indigotica Fortune (Brassicaceae). These undescribed spiro-lignans with a unique spiro[dienone-tetrahydrofuran] molecular core. [Display omitted] • Three undescribed spiro-lignans were isolated from Isatis indigotica Fortune. • The structure elucidation was achieved by quantum chemical calculation. • Isatispironeols A-B have a unique spiro[dienone-tetrahydrofuran] molecular core. • These spiro-lignans showed comparable neuroprotective effects. • (−)-isatispironeol A possessed greater AChE inhibitory activity. [ABSTRACT FROM AUTHOR]

A bioactivity-guided fractionation on the phenolic fractions from the peeled stems of Syringa pinnatifolia Hemsl., one of representative Mongolian folk medicine in China, led to the isolation and structural determination of 11 undescribed lignans and 12 known ones. These lignans cover diverse types, among them syringanones A and B represent an unprecedented carbon skeleton (proposed syringanane) and alashanenol A possesses a rare bicyclo [3.3.1]nonadienemethanol core. Their structures were established by extensive spectroscopic data analysis, X-ray diffraction, and quantum chemical calculations. All isolates were evaluated for their cardioprotective activities on H9c2 cardiomyocytes in vitro. The results showed that five lignans exhibited the protective effects against hypoxia-induced injury at the concentrations of 1.2–40 μM and six lignans exhibited anti-oxidative stress injury at 10–40 μM. These findings account to some extend for the traditional therapeutic effects of S. pinnatifolia for the treatment of ischemic heart diseases in clinic. Eleven undescribed lignans and twelve known ones were isolated from the stems of Syringa pinnatifolia Hemsl. by a bioactivity-guided approach. Their cadioprotective activities on H9c2 cells were evaluated. [Display omitted] • Eleven undescribed lignans were isolated from the stems of Syringa pinnatifolia. • Their structures with absolute configurations were completely resolved. • Syringanones A and B represent an unprecedented carbon skeleton. • Alashanenol A possesses a rare bicyclo [3.3.1]nonadienemethanol core. • These lignans exhibited cadioprotective effects on H9c2 cells. [ABSTRACT FROM AUTHOR]

Three highly oxygenated norbisabolane sesquiterpenoid glycosides (glochiwilsonosides A-C), five benzofuran lignans (glochiwilsonises A-E) and a phenolic glycoside (glochiwilsophe-noside), together with forty-one known compounds, were isolated from the roots of Glochidion wilsonii Hutch. The chemical structures of the compounds were identified by spectroscopic methods and previous literature data. Glochiwilsonoside A displayed anti-proliferative activity on A-549 and RAW 264.7 cell lines with an IC 50 value of 34.5 ± 0.9 μM and CC 50 value of 16.0 ± 0.9 μM, respectively. Twenty-three known compounds were reported from the genus Glochidion for the first time, and the chemotaxonomic characteristics of the isolated compounds were also summarized. The bisabolane/norbisabolane-type sesqui-terpenoid derivatives could be used as chemotaxonomic markers for G. wilsonii. Fifty compounds (including three undescribed highly oxygenated norbisabolane sesquiterpenoid glycosides, six undescribed compounds and forty-one known compounds) were isolated from the roots of Glochidion wilsonii Hutch and identified by NMR and ECD. [Display omitted] • Three sesquiterpenoids, five lignans and a phenolic glycoside were identified. • The chemotaxonomic characteristics of the isolated compounds were summarized. • The sesquiterpenoids could be used as chemotaxonomic markers for Glochidion wilsonii. [ABSTRACT FROM AUTHOR]

The low-molar-mass (LMM) fraction, only, i.e., the GC-eluting compounds, which are mainly lignans, has been characterized in Norway spruce knotwood hydrophilic extracts previously. Of this fraction, many lignans and sesquilignans and all GC peaks supposedly representing dilignans remain unidentified. In this work, dilignans and the GC non-eluting compounds (the high-molar mass fractions, HMM) were characterized in a 7-hydroxymatairesinol-reduced knotwood ethanol extract of Norway spruce by using several fractionation and analytical techniques. A methyl tert -butyl ether (MTBE) insoluble fraction of the extract contained mainly HMM material, of which the main part was shown to consist of lignan oligomers. The oligolignans (with a molar mass up to approximately 3700 Da) seemed to be linked by 5 5′ bonds, some of them containing one or two guaiacylglycerol ether units linked to the lignan by β O 4 or β 5 bonds. Several oligolignans were identified or tentatively identified. The MTBE soluble fraction, which accounted for the major part (81%) of the extract, contained mainly LMM material (lignans, sesqui- and dilignans). The part of the HMM material in the MTBE soluble fraction that was easily isolable (2%) seemed to contain polymers of fatty acids and alcohols, resin acids, and sterols. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) constitute a small population of undifferentiated cells within a tumor that have the ability to self-renew and drive tumor formation, thus behaving as cancer-initiating cancer cells. Therapeutic interventions that eliminate CSCs are necessary to completely cure patients, since CSCs are a crucial source of tumor recurrence and metastasis. An induced CSC-like (iCSCL) model was recently established using induced pluripotent stem cells (iPSCs). In this study, a natural product—eucommicin A—was identified from Eucommia ulmoides leaves by screening for anti-CSC activity using the iCSCL model. Its structure was elucidated by spectroscopic methods as a quinic acid diester of 3,4,3′,4′-tetrahydroxy-β-truxinic acid. Eucommicin A exhibited selective anti-CSC activity and inhibited tumor sphere formation by iCSCL cells. The results of this study suggest that eucommicin A could serve as a lead compound in the development of drugs to abrogate the stemness and self-renewal ability of CSCs. [ABSTRACT FROM AUTHOR]

Four phenylpropanoid glucosides ( 1 – 4 ) and five lignan glycosides ( 5 – 9 ) were isolated from the aerial parts of Lespedeza cuneata , together with three known lignan glycosides ( 10 – 12 ). Their structures were elucidated on the basis of spectroscopic analyses, and the absolute configurations of compounds 5 – 9 were determined from the CD spectra. In addition, the compounds were tested for their ability to activate the transcription effect on xbp1 promoter. Compounds 4 , 5 , 7 , 9 , 10 , and 12 could activate the transcription of xbp1 to varying degrees, with EC 50 values ranging from 0.18 to 0.64 μM. [ABSTRACT FROM AUTHOR]

Nine undescribed compounds, together with 21 known components, were isolated from the fresh roots of Rehmannia glutinosa. Their structures were elucidated based on spectroscopic data analysis, and the absolute configurations of undescribed compounds were determined by comparison of their calculated and experimental electronic circular dichroic (ECD) spectra and interpretation of their optical rotation data. The α -glucosidase inhibitory effects of the isolated compounds were investigated and all of them exhibited slightly inhibitory activities. [Display omitted] • Nine undescribed compounds were isolated from the fresh roots of Rehmannia glutinosa. • The structures were established based on spectroscopic data and ECD spectra analyses. • Triterpenoids reported in the paper were rarely isolated from this genus. [ABSTRACT FROM AUTHOR]

Lignans, with various biological activities, such as antitumor, antioxidant, antibacterial, and antiviral activities, are widely distributed in nature and mainly exist in the xylem of plants. In this paper, we summarized the structures and bioactivities of lignans reported in recent years (2019–2021) from five parts, including (1) a summary and classification of newly reported compounds; (2) the pharmacological activities of lignans; (3) molecular resources and activity distribution; (4) the structure-activity relationships; and (5) the clinical application of lignans. This review covers all undescribed compounds that were reported within the covered period of time and all bioactivity data about previously isolated lignans. The distribution of lignans in different plants and families is visualized, which improves the efficiency of searching for specific molecules. The diverse activities of different types of lignans provide an important reference for the rapid screening of these compounds. Discussion about the structure-activity relationships of lignans provides a direction for the structural modification of skeleton molecules. Combined with the clinical application of such molecules, this work will provide a valuable reference for pharmaceutical chemists. [Display omitted] • 356 undescribed lignans and major activities between 2019 and 2021 were reviewed. • "Norlignans" and "polymeric lignans" are summarized for the first time. • Molecular resources and activity distribution are visualized. • Structure-activity relationship analysis narrows the scope of activity screening. • The clinical application of representative lignans is presented for the first time. [ABSTRACT FROM AUTHOR]

One undescribed diterpenoid illisimonone A, four undescribed sesquiterpenes named (±)-simonones A, simonterpenoids A and B, and two undescribed lignans, illisimonins A and B, along with five known compounds were isolated from the fruits of Illicium simonsii. Their structures were elucidated by extensive spectroscopic data. The absolute configuration of illisimonone A was determined by single-crystal X-ray diffraction analysis. Illisimonone A showed potential antiviral activity against the Coxsackie B3 virus, with an IC 50 value of 3.70 μM. Illisimonin B and henrylactone A showed potential neuroprotective effects against oxygen-glucose deprivation induced cell injury in SK-N-SH cells, with survival rates of 57.6%, 58.0%, respectively. Seven undescribed compounds, together with five known compounds were isolated from Illicium simonsii Maxim. Their antiviral and neuroprotective activities were evaluated. [Display omitted] • Seven undescribed compounds were isolated from the fruits of Illicium simonsii. • The absolute configuration of undescribed compounds were determined by single-crystal X-ray diffraction analysis, ECD calculation, and a modified Mosher's method. [ABSTRACT FROM AUTHOR]

Arctium lappa is a well-known traditional medicinal plant in China (TCM) and Europe that has been used for thousands of years to treat arthritis, baldness or cancer. The plant produces lignans as secondary metabolites, which have a wide range of bioactivities. Yet, their antiaging potential has not been explored. In this study, we isolated six lignans from A. lappa seeds, namely arctigenin, matairesinol, arctiin, (iso)lappaol A, lappaol C, and lappaol F. The antioxidant and antiaging properties of the isolated lignans were studied using Caenorhabditis elegans as a relevant animal model. All lignans at concentrations of 10 and 100 μM significantly extended the mean life span of C. elegans . The strongest effect was observed with matairesinol, which at a concentration of 100 μM extended the life span of worms by 25%. Additionally, we observed that five lignans are strong free radical-scavengers in vitro and in vivo and all lignans can improve survival of C. elegans under oxidative stress. Furthermore, the lignans can induce the nuclear translocation of the transcription factor DAF-16 and up-regulate its expression, suggesting that a possible underlying mechanism of the observed longevity-promoting activity of lignans depends on DAF-16 mediated signaling pathway. All lignans up-regulated the expression of jnk-1 , indicating that lignans may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade. Our study reports new antiaging activities of lignans, which might be candidates for developing antiaging agents. [ABSTRACT FROM AUTHOR]

Due to their pronounced cytotoxic activity, a number of aryltetralin lignans (ATLs), such as podophyllotoxin (PTOX), are used as antitumor compounds. The production of such molecules from entire plants or plant cell-tissue-organ cultures is thus of interest to the pharmaceutical industry. Hairy root cultures constitute a good tool not only for phytochemical production but also for investigating plant secondary metabolism. This work reports on the growth and ATL biosynthesis in two hairy root cultures of Linum album Kotschy ex Boiss. and Linum flavum . The kinetics of accumulation of the intermediates of MPTOX biosynthesis and of their glucosylated forms are described over a 21-day period of growth. An accumulation of non-glucosylated forms of the ATLs during the exponential phase of the cultures is followed by an accumulation of the glucosylated forms during the stationary phase. Our results show a strong coordination of the biosynthetic paths derived from deoxypodophyllotoxin via deoxypodophyllotoxin 6-hydroxylase and deoxypodophyllotoxin 7-hydroxylase, and a coordinated glucosylation of podophyllotoxin, methoxypodophyllotoxin, and 5′-demethoxymethoxypodophyllotoxin. Furthermore, our results suggest an important role of β-peltatin-6-glucoside formation in the control of ATL accumulation in Linum hairy root cultures. [ABSTRACT FROM AUTHOR]

Seven undescribed lignans, equiselignan A–F, and six undescribed terpenoids, equiseterpenoid A–E (including two pairs of enantiomers, (+/−)-equiselignan A and (+/−)-equiseterpenoid E), were isolated from the stems of Ephedra equisetina Bunge. Their structures were elucidated by spectroscopic methods, and the absolute configurations of the undescribed compounds were determined by interpretation of their electronic circular dichroic (ECD) and optical rotation data. In β -hexosaminidase (β -Hex) release assay, anti-asthmatic activities of all of the compounds were evaluated by releasing β -Hex in C48/80-induced RBL-2H3 cells. The β -Hex release rates of equiselignan B and equiseterpenoid B were 0.86 ± 0.094 and 0.86 ± 0.012 by comparing with model group, whereupon equiselignan B and equiseterpenoid B exhibited significant anti-asthmatic activities. [Display omitted] • Thirteen undescribed compounds were isolated from the stems of E. equisetina. • Their structures were elucidated by NMR and mass spectrometry. • The absolute configurations were deduced by interpretation of ECD and [α] data. • The anti-asthmatic activities of all the isolated compounds were evaluated. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the aerial parts obtained from the Turkish plant Centaurea kotschyi subsp. persica led to the isolation of nine sesquiterpene lactones belonging to the guaiane class, including the undescribed kotschyols A and B, a monoterpene lactone (daphnauranin E), four known lignans (matairesinol, matairesinoside, arctiin and arctigenin) and an undescribed dihydrobenzofuran neolignan (4- O -glucosylcrataegifin A). The structures of these compounds were defined by spectroscopic analysis, including ECD and 1D/2D NMR, and chemical conversion. Spurred from the traditional use of C. kotschyi subsp. persica and previous reports on the activity of its extracts, the isolated compounds were evaluated for their hypoglycaemic activity disclosing the bioactive components. Aerial parts of Centaurea kotschyi subsp. persica contain the undescribed sesquiterpene lactones kotschyols A and B and the dihydrobenzofuran neolignan 4- O -glucosylcrataegifin A. All the isolated compounds were evaluated for their hypoglycaemic activity disclosing the bioactive components. [Display omitted] • The aerial parts of the Turkish plant Centaurea kotschyi subsp. persica have been analyzed. • Two new guaianolides, named kotschyols, and a new neolignane have been isolated. • Detailed structural characterization of the isolated compounds is reported. • Isolated compounds have been evaluated for their hypoglycaemic activity. [ABSTRACT FROM AUTHOR]

Parasitic diseases continue to be a major worldwide health problem, and there is an urgent need for development of therapeutic drugs. This paper describes synthesis of dehydrodiferulic acid dilactone 1 and dehydrodisinapic acid dilactone 2 furofuran lignans by oxidative coupling of ferulic and sinapic acids, respectively. Their schistosomicidal, trypanocidal, and leishmanicidal activities were evaluated in vitro against Schistosoma mansoni adult worms, trypomastigote and amastigotes forms of Trypanosoma cruzi , and promastigote forms of Leishmania amazonensis . Compound 1 did not display significant schistosomicidal activity, but it presented potent trypanocidal activity, since it induced death of trypomastigotes and amastigotes with IC 50/24h of 9.3 μM and 7.3 μM, respectively. Compound 2 had slight trypanocidal and schistosomicidal activities. None of the compounds were active against L. amazonensis . These results demonstrated that furofuran lignans are potentially useful for anti-parasitic drugs development and should be further investigated. [ABSTRACT FROM AUTHOR]

Systematic phytochemical investigations on Abies delavayi afforded 110 compounds, including 49 terpenoids, 13 lignans, 20 flavonoids, three coumarins, and 25 other chemical constituents. By detailed analysis of one- and two-dimensional NMR spectroscopic and high-resolution mass spectrometric data, 10 previously unreported compounds were identified: they comprised three sesquiterpenoids, two diterpenoids, one triterpenoid, one monoterpenoid, one flavonoid, and two phenols. These 10 compounds and some previously known ones were subjected to two cytotoxic bioassays against three human tumor cell lines and NO production inhibition on RAW264.7 macrophages, respectively. (25R)-24,25-Dihydroabieslactone had the strongest cytotoxic activity against Colo-205 cells with an IC50 value of 19.0±3.7μg/mL. (+)-T-cadinol, 8,11,13-abietatrien-15-ol-18-yl acetate, 18-acetoxy-13-epi-manool, imperatorin, bergapten, and 5,7-O-dimethyl poriol exhibited weak inhibitory activity against LPS-induced NO production in RAW264.7 macrophages with IC50 values of approximately 50μg/mL. [ABSTRACT FROM AUTHOR]

Highlights: [•] Fourteen dibenzocyclooctadiene lignans have been isolated from Schisandra Fructus. [•] The structures of four new lignans were elucidated. [•] Eleven lignans inhibit on NO release in LPS-induced BV2 microglia cells. [Copyright &y& Elsevier]

To investigate the biosynthetic pathways and regulatory mechanisms of lignans in plants, the actual distributions of lignans and lignan glucosides in flash-frozen stems of Ginkgo biloba L. (Ginkgoaceae) were studied using cryo time-of-flight secondary ion mass spectrometry coupled with scanning electron microscopy (cryo-TOF-SIMS/SEM). Four lignans and four lignan glucosides were successfully characterized. Quantitative HPLC measurements were conducted on serial tangential sections of freeze-fixed ginkgo stem to determine the amount and approximate distribution of lignan and lignan glucosides. (−)-Olivil 4,4′-di- O -β- d -glucopyranoside (olivil DG) was the most abundant lignan glucoside in ginkgo and was distributed mainly in the phloem, ray parenchyma cells, and pith. The comparative accumulation of olivil DG revealed its possible transport pathways and storage sites in ginkgo. Although not all relevant enzymes have been identified, understanding the distributions of lignan and lignan glucosides in ginkgo stems provides significant insight into their biological functions. [Display omitted] • Lignans and lignan glucosides were visualized by cryo-TOF-SIMS/SEM. • (−)-olivil 4,4′-di- O -β-D-glucopyranoside was the most abundant lignan glucosides in ginkgo, and was distributed mainly in the phloem region, pith, and ray parenchyma cells in the mature xylem region. • (−)-olivil 4,4′-di- O -β-D-glucopyranoside might be an important intermediate and storage form in the ginkgo lignan biosynthetic pathway. • Specialised metabolites were commonly accumulated in the parenchyma cells. [ABSTRACT FROM AUTHOR]

In our ongoing effort to investigate active specialised metabolites from genus Glandularia, phytochemical studies on the ethanolic extract of Glandularia × hybrida (Groenl. & Rümpler) G.L. Nesom & Pruski leaves resulted in the isolation of three undescribed compounds, a dibenzylbutyrolactolic lignan and two echinocystic acid based triterpenoid saponins, in addition to two known compounds. Interestingly, this study reports isolation of chemo-systematically valuable specialised metabolites for the first time from the genus under investigation. Additionally, the isolated metabolites were evaluated for their iNOS inhibition and cytotoxic activities using a combination of in silico and in vitro studies. The pharmacokinetics properties (ADMET) of some of the isolated compounds were determined using pkCSM-pharmacokinetics server. Molecular docking analysis showed that saponin compound possesses higher negative score (−9.59 kcal/mol) than the lignan compound (−6.56 kcal/mol). The isolated compounds also showed iNOS inhibition activity with IC 50 values ranging between 6.6 and 49.7 μM and significant cytotoxic activity against a series of cell lines including SK-MEL, KB, BT-549, SK-OV-3, LLC-PK1 and VERO cells. Hence, this study reveals that specialised metabolites from G. hybrida plant are of significant anti-inflammatory and cytotoxicity potentials. [Display omitted] • Isolation of three undescribed compounds from Glandularia × hybrida leaves with chemo-taxonomical significance. • Molecular docking of the isolated compounds to study their potential as iNOS inhibitors. • Determination of pharmacokinetics properties (ADMET) of some of the isolated compounds. • Isolated compounds were evaluated for their cytotoxic and iNOS inhibitory activities. [ABSTRACT FROM AUTHOR]