Lignans have been established as a privileged scaffold in drug discovery,particularly in anticancer and antioxidant properties.Concise and efficient construction of lignans and their derivatives in a single operation ...Lignans have been established as a privileged scaffold in drug discovery,particularly in anticancer and antioxidant properties.Concise and efficient construction of lignans and their derivatives in a single operation holds great medicinal significance for structure-activity relationship studies yet remains challenging.Drawing inspiration from the biosynthesis of lignans,we present a general,high-step-economy palladium-catalyzed reaction that converts simple chemical feedstocks into dehydrodibenzylbutyrolactone lignans through the in-situ construction and coupling of two phenylpropanoid molecules.The diversity of organoboronic acids and the editability of enyne provide a powerful platform for the rapid construction of lignan libraries,featuring 82 lignans analogs,collective syntheses of 10 distinct lignan skeletons,and 13 hybrid molecules combining pharmacophore fragments with drug and derivatives.The subtle combination of phosphine ligands with quinones for switching chemoselectivity is vital to the success of this protocol.展开更多
Twelve lignans(1-12)isolated from Amomum tsao-ko leaves were evaluated for the inhibitory effects againstα-glucosidase and PTP1B.Compounds 1-4 and 10 showed inhibition on α-glucosidase with inhibitory ratios ranging...Twelve lignans(1-12)isolated from Amomum tsao-ko leaves were evaluated for the inhibitory effects againstα-glucosidase and PTP1B.Compounds 1-4 and 10 showed inhibition on α-glucosidase with inhibitory ratios ranging from53.8%to90.0%,while compound10 demonstrated 56.1% inhibition on PTP1B at 200μM.Notably,erythro-5-methoxy-dadahol A(2)and threo-5-methoxy-dadahol A(3)displayed obvious inhibition on α-glucosidase with IC50 values of 33.3μM and 22.1μM,significantly outperforming acarbose(IC_(50)=344.0μM).Kinetic study revealed that compound 3 maintained amixed-typemode,engaging with both free enzyme and enzyme-substrate complex via noncompetitive and uncompetitive mechanisms.Molecular docking simulations further clarified its interactions with the key residues of Trp402,Lys400,and Gly361 in the catalytic pocket.In vivo evaluation demonstrated that oryzativol A(1)showed dose-dependent hypoglycemic effects in an oral starch tolerance test,reducing postprandial blood glucose levels(AUC)by 21.1%(20 mg/kg)and 24.9%(40 mg/kg).These results highlight the potential of lignans in A.tsao-ko as α-glucosidase inhibitors for managing type 2 diabetes,warranting further exploration of their therapeutic potential.展开更多
Dietary supplementation with plant-derivedα-linolenic acid(ALA)has the potential to alleviate the insufficient intake of global n-3 long-chain polyunsaturated fatty acids(n-3 LCPUFAs),but faces the bottleneck of high...Dietary supplementation with plant-derivedα-linolenic acid(ALA)has the potential to alleviate the insufficient intake of global n-3 long-chain polyunsaturated fatty acids(n-3 LCPUFAs),but faces the bottleneck of highβ-oxidation consumption,oxidative susceptibility,and low conversion efficiency.The current study investigated how flax lignans with different degrees of polymerization and glycosylation affect the conversion of ALA to n-3 LCPUFAs in mice over 35 days of administering sunflower phospholipid-stabilized flaxseed oil nanoemulsions.Results showed that flax lignan macromolecules(FLM)increased hepatic protein expression of elongase of very long chain fatty acid 5(Elovl5,24.2%)and fatty acid desaturase 2(Fads2,44.7%),thereby positively regulating ALA conversion pathways and raising serum eicosapentaenoic acid(EPA)levels(52.7%)via liver lipid re-efflux.Secoisolariciresinol diglucoside(SDG)enhanced ALA desaturation by upregulating hepatic protein expression of Fads1(30.4%)and Fads2(45.6%),increasing serum EPA levels(55.9%)and hepatic docosahexaenoic acid(DHA)levels(10%).Secoisolariciresinol(SECO)elevated hepatic protein expression of Elovl2(30.7%),Elovl5(11.7%),Fads1(37.9%),and Fads2(24.1%),but also increased carnitine palmitoyltransferase 1a(45.2%),leading to decreased ALA,EPA,and DHA levels in serum and liver.Therefore,in comparison,FLM and SDG emerge as the dominant structural units that positively regulate the conversion of ALA.These findings lay a groundwork for designing precise dietary delivery systems to enhance the conversion to n-3 LCPUFAs.展开更多
Five previously undescribed diterpenoids,named succipenoids D‒H(1‒5),along with four undescribed lignans,named succignans A‒D(6‒9),were isolated from the dichloromethane extract of Chinese medicinal succinum.Compounds...Five previously undescribed diterpenoids,named succipenoids D‒H(1‒5),along with four undescribed lignans,named succignans A‒D(6‒9),were isolated from the dichloromethane extract of Chinese medicinal succinum.Compounds 1‒5 were characterized as nor-abietane diterpenoids,while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units.The structures of these novel compounds,including their absolute configurations,were determined through spectroscopic and computational methods.Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis,includingα-smooth muscle actin(α-SMA),collagen I,and fibronectin in transforming growth factor-β1(TGF-β1)induced normal rat kidney proximal tubular epithelial cells(NRK-52e).展开更多
The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum(I.dunnianum)resulted in the isolation of five pairs of new lignans(1–5),and 7 known analogs(6–12).The separation of enantiomer mi...The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum(I.dunnianum)resulted in the isolation of five pairs of new lignans(1–5),and 7 known analogs(6–12).The separation of enantiomer mixtures 1–5 to 1a/1b–5a/5b was achieved using a chiral column with acetonitrile−water mixtures as eluents.The planar structures of 1–2 were previously undescribed,and the chiral separation and absolute configurations of 3–5 were reported for the first time.Their structures were determined through comprehensive spectroscopic data analysis[nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass(HR-ESI-MS),infrared(IR),and ultraviolet(UV)]and quantum chemistry calculations(ECD).The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide(LPS)-stimulated BV-2 cells.Compounds 1a,3a,3b,and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner.Western blot and real-time polymerase chain reaction(PCR)assays revealed that 1a down-regulated the messenger ribonucleic acid(mRNA)levels of tumor necrosis factorα(TNF-α),interleukin-6(IL-6),COX-2,and iNOS and the protein expressions of COX-2 and iNOS.This research provides guidance and evidence for the further development and utilization of I.dunnianum.展开更多
Five new furofuran lignans and their derivatives,(-)-glaberide I 4-O-β-D-glucopyranoside(1a),(+)-glaberide I 4-O-β-D-glucopyranoside(1b),(+)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside(2a),(-)-glaberide I 7&#...Five new furofuran lignans and their derivatives,(-)-glaberide I 4-O-β-D-glucopyranoside(1a),(+)-glaberide I 4-O-β-D-glucopyranoside(1b),(+)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside(2a),(-)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside(2b),and(-)-isoeucommin A(3b),along with fifteen known analogs were isolated from the stems of Dendrobium'Sonia'.These compounds were classified into ten pairs of enantiomers or diastereoisomers via chiral resolution,and their structures were determined based on extensive spectroscopic data.Their absolute configurations were determined by hydrolysis,comparison of experimental and calculated electronic circular dichroism(ECD)data,and single-crystal X-ray diffraction analysis.The isolates were evaluated for their ability to inhibit nitric oxide(NO)production in RAW264.7 cells.Among them,syringaresinol(5)exhibited prominent inhibition activity,with an IC50 value of 28.4±3.0μmol·L~(-1),and there was a slight difference between 5a,5b and the racemic mixture 5.展开更多
As a traditional Chinese herbal medicine,Schisandrae Chinensis Fructus(SC)has been used in medicine and food industry due to its health care and therapeutic effects.Over the past 20 years,the use of SC and its active ...As a traditional Chinese herbal medicine,Schisandrae Chinensis Fructus(SC)has been used in medicine and food industry due to its health care and therapeutic effects.Over the past 20 years,the use of SC and its active ingredient lignans in the prevention and treatment of liver diseases has been increasing,and their hepatoprotective effects has increased the interest of the public and academia.Therefore,in the present work,we first determined the effectiveness of SC in the treatment of liver diseases such as metabolic associated fatty liver disease,alcoholic liver disease,cholestatic liver disease and acute liver injury.Subsequently,the pharmacological effects and molecular mechanisms of lignans,the active components of SC,for liver disease treatment were comprehensively summarized for the first time.The results showed that the lignans in SC could achieve hepatoprotective effects by regulating lipid metabolism,anti-fibrosis,anti-inflammation,anti-oxidation,anti-tumor and regulating bile acid metabolism.The mechanism mainly involved adenosine 5’-monophosphate-activated protein kinase,endoplasmic reticulum stress,sterol regulatory element binding protein 1c,autophagy,transforming growth factor-β,mitogen-activated protein kinase,microRNA,nuclear factor kappa-B,nuclear factor erythroid-2-related factor 2,heat shock proteins and pregnane X receptor signaling pathways.These results can lay a scientific foundation for the development of hepatoprotective drugs or functional foods from SC/lignans.展开更多
In this study,two new kaurane diterpenes(16,17),together with 12 lignans(1-12),a triterpene(15),and two other compounds(13,14)were isolated from the woods of Agathis dammara.The structure of the new compound was deter...In this study,two new kaurane diterpenes(16,17),together with 12 lignans(1-12),a triterpene(15),and two other compounds(13,14)were isolated from the woods of Agathis dammara.The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy,and its absolute configuration was determined by electronic circular dichroism(ECD)exciton chirality method.Compounds 5,11,14 exhibit significant hypoglycaemic activity in zebrafish,and their mechanism of action is to enhance glucose uptake in zebrafish.展开更多
The identification of natural, plant-derived compounds with pesticidal properties is crucial for developing environmentally sustainable alternatives to synthetic pesticides. In this study, four major lignans—dihydroc...The identification of natural, plant-derived compounds with pesticidal properties is crucial for developing environmentally sustainable alternatives to synthetic pesticides. In this study, four major lignans—dihydroclusin, cubebin, clusin, and yatein—were isolated from the crude extract of Piper cubeba fruit. Phytotoxicity assays revealed herbicidal activity against Agrostis stolonifera, with dihydroclusin and clusin exhibiting the highest efficacy, inhibiting seed germination by 50% and showing IC50 values of 2.9 µM and 45 µM, respectively, against Lemna paucicostata. Additionally, all compounds, except dihydroclusin, demonstrated fungicidal activity against the strawberry anthracnose pathogen Colletotrichum fragariae. Moreover, only dihydroclusin exhibited larvicidal activity against Aedes aegypti, causing 96% mortality of mosquito larvae at the 100-ppm concentration tested. These findings highlight the broad-spectrum bioactivity of Piper cubeba lignans, suggesting their potential as alternative agents of synthetic pesticides for managing agricultural pests.展开更多
To study the antioxidant constituents from the stems of Dendrobium nobile, and to discuss theft structure-activity relationship. Compounds were isolated from a 60% ethanolic extract by various chromatographic techniqu...To study the antioxidant constituents from the stems of Dendrobium nobile, and to discuss theft structure-activity relationship. Compounds were isolated from a 60% ethanolic extract by various chromatographic techniques and were identified by spectral analysis. The antioxidant activities of compounds were evaluated by DPPH free radical scavenging assay. Five phenanthrenes and four lignans were obtained from the active fractions ofD. nobile. Their structures were identified as fimbriatone （1）, confusarin （2）, flavanthrinin （3）, 2,5-dihydroxy-4,9-dimethoxyphenanthrene （4）, 3,7-dihydroxy-2,4-dimethoxyphenanthrene （5）, syringaresinol （6）, pinoresinol （7）, medioresinol （8） and lirioresinol-A （9）, respectively. Compounds 2 and 6 exhibited more potent DPPH scavenging activities than vitamin C. All the above compounds were reported from this plant for the first time, and compounds 3, 4 and 9 were reported for the first time from the genus of Dendrobiurn. For all phenanthrenes and lignans, an electron-donating methoxyl group in the ortho position to the phenolic hydroxyl group exhibits enhanced antioxidant activities.展开更多
A new lignan glycoside, named （7S,8R,8＇R）-（-）-lariciresinol-9-O-a-L-rhamnopyranosyl （1-2） 13-D-glucopyranoside （1）,was isolated from the ethanol extract ofPilea cavaleriei Levi subsp, cavaleriei, together wit...A new lignan glycoside, named （7S,8R,8＇R）-（-）-lariciresinol-9-O-a-L-rhamnopyranosyl （1-2） 13-D-glucopyranoside （1）,was isolated from the ethanol extract ofPilea cavaleriei Levi subsp, cavaleriei, together with 17 known lignans （2-18）. The structuresof these compounds were elucidated by extensive spectroscopic analysis, including 1D NMR, 2D NMR and HR-ESI-MS.All the compounds were obtained from the genus Pilea for the first time.展开更多
Seven known dibenzocyclooctadiene lignans,tigloylgomisin P(1), angeloylgomisin P(2),gomisin A(3),Schizandrin(4),angeloylgomisin H(5),gomisin B(6) and R(+)-gomisin M_1(7)were isolated from Kadsura heteroclita.The confo...Seven known dibenzocyclooctadiene lignans,tigloylgomisin P(1), angeloylgomisin P(2),gomisin A(3),Schizandrin(4),angeloylgomisin H(5),gomisin B(6) and R(+)-gomisin M_1(7)were isolated from Kadsura heteroclita.The conformation of tiglolylgomisin P(1)was established by 2D NMR techniques.Using[~3H]platelet activating factor(PAF)binding to human platelet membrane assay,(1),(2)and(7)showed PAF receptor antagonistic activities.展开更多
Four new seco-dibenzocyclooctadiene lignans,kadlongilignans A-D(1-4),consisting of a rare 6,7-seco-(1),two 15,16-seco-(2 and 3) and a 9,10-seco-dibenzocyclooctadiene(4) lignans,were isolated from the roots of Kadsura ...Four new seco-dibenzocyclooctadiene lignans,kadlongilignans A-D(1-4),consisting of a rare 6,7-seco-(1),two 15,16-seco-(2 and 3) and a 9,10-seco-dibenzocyclooctadiene(4) lignans,were isolated from the roots of Kadsura longipedunculata.Their structures were elucidated by spectroscopic analysis,including extensive NM R,MS and ECD(electronic circular dichroism) spectra.Compounds 3 and 4 exhibited potent inhibitory activities against NO(nitric oxide) production of LPS(lipopolysaccharide)-induced murine macrophages with the inhibition rates of 36.3% and 26.9%,respectively.展开更多
This study was aimed to determine whether flaxseed lignans could affect the growth of skeletal muscle in male animals and its possible mechanisms. The impact of flaxseed lignans on the skeletal muscle in male rats was...This study was aimed to determine whether flaxseed lignans could affect the growth of skeletal muscle in male animals and its possible mechanisms. The impact of flaxseed lignans on the skeletal muscle in male rats was determined in vivo. Flaxseed lignans （50 ppm） and daidzein （5 ppm） were added into the basal diets, respectively. The concentrations of serum lignans and daidzein were measured by high performance liquid chromatography （HPLC）, and the serum growth hormone and testosterone （T） levels were analyzed by radioimmunoassay （RIA）, and the expression of estrogen receptor β （ER β） in the soleus muscle and hypothalamus were determined by reverse-transcription polymerase chain reaction （RT-PCR）. Flaxseed lignans and daidzein could significantly improve the feed efficiency and facilitate the weight gain of the femoral muscle in male rats. The ratio of RNA to DNA in the muscles and serum T levels was remarkably increased, whereas, the urea nitrogen concentrations were significantly decreased by flaxseed lignan and/or its metabolites and daidzein. Meanwhile, the expression of ER β in soleus muscle and hypothalamus were both upgraded by the two phytoestrogens. Flaxseed lignan promoted the growth of male rats, and it might be by regulating serum T levels by binding to ER β in the hypothalamus. In turn, it depressed the catabolism of protein and promoted the hypertrophy of skeletal muscle ceils.展开更多
A phytochemical investigation on the aerial parts of Artemisia brachyloba led to the isolation of 13 compounds（1-13） for the first time, including eight lignans（1-8） and five flavonoids（9-13）. The structures of ...A phytochemical investigation on the aerial parts of Artemisia brachyloba led to the isolation of 13 compounds（1-13） for the first time, including eight lignans（1-8） and five flavonoids（9-13）. The structures of the isolated compounds were elucidated by analysis of the NMR spectroscopic data and comparison with the literature. The 1 H and 13 C NMR data of 1 were fully assigned for the first time by the 2 D NMR analysis. All the isolates were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccharide-challenged BV-2 microglial cells.展开更多
A new sesquilignan, 7＇,8＇-didehydroherpetotriol （1）, and a new lignan glycoside, （＋）-isolariciresinol-9＇-O-α-L-rhamnopyra- nosy1-（1→6）-[3-D-glucopyranoside （2）, were isolated from the branches of Diptero...A new sesquilignan, 7＇,8＇-didehydroherpetotriol （1）, and a new lignan glycoside, （＋）-isolariciresinol-9＇-O-α-L-rhamnopyra- nosy1-（1→6）-[3-D-glucopyranoside （2）, were isolated from the branches of Dipteronia dyeriana. Their structures were elucidated by spectroscopic methods and chemical evidence. Compound 1 possessed inhibitory activity against human leukaemia K562 cells with an IC50 value of 39 μmol/L.展开更多
Herpetospermum caudigerum lignans(HTL),one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects,has limited clinical applications because of poor aqueous solubility and low bioavailability.B...Herpetospermum caudigerum lignans(HTL),one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects,has limited clinical applications because of poor aqueous solubility and low bioavailability.Both herpetrione(HPE)and herpetin(HPN)are the most abundant ingredients in HTL and exhibit weak acidity.The purpose of the present study was to produce dried preparations of HTL(composed of HPE and HPN)nanosuspensions(HTL-NS)with high redispersibility using lyophilization technology.The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions,and critical formulation and process parameters affecting the characteristics of HTL-NS were optimized.The resultant products were characterized by particle size analysis,SEM,XRD,stability,solubility,dissolution and in vivo bioavailability.HTL-NS showed near-spherical-shaped morphology and the size was 243 nm with a narrow PDI value of 0.187.The dried preparations with a relatively large particle size of 286 nm and a PDI of 0.215 were achieved by using 4%(W/V)mannitol as cryoprotectants,and had a better stability at 4 or 25 oC for 2 months,compared to HTL-NS.In the in vitro test,the dried preparations showed markedly increased solubility and dissolution velocity.Besides,in the in vivo evaluation,it exhibited significant increases in AUC0–t,C_(max),MRT and a decrease in T_(max),compared to the raw drug..In conclusion,our results provide a basis for the development of a drug delivery system for poorly water-soluble ingredients with p H-dependent solubility.展开更多
The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills(GNDP) by transforming lignans of Herpetospermum caudigerum(HL) composed of herpetrione(HPE) and herpetin(H...The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills(GNDP) by transforming lignans of Herpetospermum caudigerum(HL) composed of herpetrione(HPE) and herpetin(HPN) into nanosuspension(HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles(HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015 J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy(PCS), zeta potential measurement, and scanning electron microscopy(SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC0–t, Cmax and decrease in Tmax when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.展开更多
Twenty-one lignans including three new ones(1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1 D and 2 D NMR analysis. Th...Twenty-one lignans including three new ones(1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1 D and 2 D NMR analysis. These compounds were evaluated for their cytotoxic and anti-HIV activities. The new secoisolariciresinol dimethyl ether acetate(13) exhibited anti-HIV-1 activity with an IC50 value of 5.27 μmol·L^-1 and a selective index(SI) value of 2.2. The known arylnaphthalene lignan procumbenoside A(3) and diphyllin(8) demonstrated inhibitory activity against HIV-1 with IC50 values of 4.95(SI > 6.2) and 0.38 μmol·L^-1(SI = 5.3), respectively.展开更多
Ten neolignans or norlignans(1-10)including eight new compounds were isolated from the whole bodies of Polyphaga plancyi Bolivar.Their structures were identified by spectroscopic data.Compounds 3,4,8,and 9 are racemat...Ten neolignans or norlignans(1-10)including eight new compounds were isolated from the whole bodies of Polyphaga plancyi Bolivar.Their structures were identified by spectroscopic data.Compounds 3,4,8,and 9 are racemates indicated by chiral HPLC analysis.Chiral separation followed by ECD calculations allowed to clarify the absolute configurations of all the antipodes.All the new compounds were evaluated for their biological properties toward extracellular matrix in rat renal proximal tubular cells,human cancer cells(K562,A549,and Huh7),EV71,ROCK2,JAK3,DDR1,and coagulation.展开更多
基金Financial support was provided by the State Key Laboratory of Pulp and Paper Engineering(No.2022PY01)the National Natural Science Foundation of China(Nos.22231002 and 21871095)the Key-Area Research and Development Program of Guangdong Province(No.2020B010188001)。
文摘Lignans have been established as a privileged scaffold in drug discovery,particularly in anticancer and antioxidant properties.Concise and efficient construction of lignans and their derivatives in a single operation holds great medicinal significance for structure-activity relationship studies yet remains challenging.Drawing inspiration from the biosynthesis of lignans,we present a general,high-step-economy palladium-catalyzed reaction that converts simple chemical feedstocks into dehydrodibenzylbutyrolactone lignans through the in-situ construction and coupling of two phenylpropanoid molecules.The diversity of organoboronic acids and the editability of enyne provide a powerful platform for the rapid construction of lignan libraries,featuring 82 lignans analogs,collective syntheses of 10 distinct lignan skeletons,and 13 hybrid molecules combining pharmacophore fragments with drug and derivatives.The subtle combination of phosphine ligands with quinones for switching chemoselectivity is vital to the success of this protocol.
基金financially supported by the Yunnan Major Scientific and Technological Program(202202AE090035)CAS Interdisciplinary Team of“Light of West China”Program(xbzg-zdsys-202405)+2 种基金the Yunnan Fundamental Research Projects(202201AV070010,202301AS070069,202402AA310003)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB1230000)the Yunnan Province Science and Technology Department(202305AH340005).
文摘Twelve lignans(1-12)isolated from Amomum tsao-ko leaves were evaluated for the inhibitory effects againstα-glucosidase and PTP1B.Compounds 1-4 and 10 showed inhibition on α-glucosidase with inhibitory ratios ranging from53.8%to90.0%,while compound10 demonstrated 56.1% inhibition on PTP1B at 200μM.Notably,erythro-5-methoxy-dadahol A(2)and threo-5-methoxy-dadahol A(3)displayed obvious inhibition on α-glucosidase with IC50 values of 33.3μM and 22.1μM,significantly outperforming acarbose(IC_(50)=344.0μM).Kinetic study revealed that compound 3 maintained amixed-typemode,engaging with both free enzyme and enzyme-substrate complex via noncompetitive and uncompetitive mechanisms.Molecular docking simulations further clarified its interactions with the key residues of Trp402,Lys400,and Gly361 in the catalytic pocket.In vivo evaluation demonstrated that oryzativol A(1)showed dose-dependent hypoglycemic effects in an oral starch tolerance test,reducing postprandial blood glucose levels(AUC)by 21.1%(20 mg/kg)and 24.9%(40 mg/kg).These results highlight the potential of lignans in A.tsao-ko as α-glucosidase inhibitors for managing type 2 diabetes,warranting further exploration of their therapeutic potential.
基金supported by grants from the National Natural Science Foundation of China(32072267)China Agriculture Research System(CARS-14)+1 种基金National Key Research and Development Program of China(2023YFD2100404)the Innovation Group Project of Hubei Province(2023AFA042).
文摘Dietary supplementation with plant-derivedα-linolenic acid(ALA)has the potential to alleviate the insufficient intake of global n-3 long-chain polyunsaturated fatty acids(n-3 LCPUFAs),but faces the bottleneck of highβ-oxidation consumption,oxidative susceptibility,and low conversion efficiency.The current study investigated how flax lignans with different degrees of polymerization and glycosylation affect the conversion of ALA to n-3 LCPUFAs in mice over 35 days of administering sunflower phospholipid-stabilized flaxseed oil nanoemulsions.Results showed that flax lignan macromolecules(FLM)increased hepatic protein expression of elongase of very long chain fatty acid 5(Elovl5,24.2%)and fatty acid desaturase 2(Fads2,44.7%),thereby positively regulating ALA conversion pathways and raising serum eicosapentaenoic acid(EPA)levels(52.7%)via liver lipid re-efflux.Secoisolariciresinol diglucoside(SDG)enhanced ALA desaturation by upregulating hepatic protein expression of Fads1(30.4%)and Fads2(45.6%),increasing serum EPA levels(55.9%)and hepatic docosahexaenoic acid(DHA)levels(10%).Secoisolariciresinol(SECO)elevated hepatic protein expression of Elovl2(30.7%),Elovl5(11.7%),Fads1(37.9%),and Fads2(24.1%),but also increased carnitine palmitoyltransferase 1a(45.2%),leading to decreased ALA,EPA,and DHA levels in serum and liver.Therefore,in comparison,FLM and SDG emerge as the dominant structural units that positively regulate the conversion of ALA.These findings lay a groundwork for designing precise dietary delivery systems to enhance the conversion to n-3 LCPUFAs.
基金supported by Shenzhen Fundamental Research Program(No.JCYJ20200109114003921).
文摘Five previously undescribed diterpenoids,named succipenoids D‒H(1‒5),along with four undescribed lignans,named succignans A‒D(6‒9),were isolated from the dichloromethane extract of Chinese medicinal succinum.Compounds 1‒5 were characterized as nor-abietane diterpenoids,while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units.The structures of these novel compounds,including their absolute configurations,were determined through spectroscopic and computational methods.Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis,includingα-smooth muscle actin(α-SMA),collagen I,and fibronectin in transforming growth factor-β1(TGF-β1)induced normal rat kidney proximal tubular epithelial cells(NRK-52e).
基金supported by the Basic Research Program of the Natural Science Fund-Frontier Leading Technology Basic Research Special Project(No.SBK2023050003)by the University Science and Technology Innovation Team of Department of Education of Guizhou Province(No.QJ[2023]099).
文摘The anti-inflammatory phytochemical investigation of the leaves of Illicium dunnianum(I.dunnianum)resulted in the isolation of five pairs of new lignans(1–5),and 7 known analogs(6–12).The separation of enantiomer mixtures 1–5 to 1a/1b–5a/5b was achieved using a chiral column with acetonitrile−water mixtures as eluents.The planar structures of 1–2 were previously undescribed,and the chiral separation and absolute configurations of 3–5 were reported for the first time.Their structures were determined through comprehensive spectroscopic data analysis[nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass(HR-ESI-MS),infrared(IR),and ultraviolet(UV)]and quantum chemistry calculations(ECD).The new isolates were evaluated by measuring their inhibitory effect on NO in lipopolysaccharide(LPS)-stimulated BV-2 cells.Compounds 1a,3a,3b,and 5a demonstrated partial inhibition of NO production in a concentration-dependent manner.Western blot and real-time polymerase chain reaction(PCR)assays revealed that 1a down-regulated the messenger ribonucleic acid(mRNA)levels of tumor necrosis factorα(TNF-α),interleukin-6(IL-6),COX-2,and iNOS and the protein expressions of COX-2 and iNOS.This research provides guidance and evidence for the further development and utilization of I.dunnianum.
基金financially supported by the Program of Shanghai Municipal Commission of Health and Family Planning[No.ZY(2021-2023)-0215]。
文摘Five new furofuran lignans and their derivatives,(-)-glaberide I 4-O-β-D-glucopyranoside(1a),(+)-glaberide I 4-O-β-D-glucopyranoside(1b),(+)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside(2a),(-)-glaberide I 7'-ethoxy-4-O-β-D-glucopyranoside(2b),and(-)-isoeucommin A(3b),along with fifteen known analogs were isolated from the stems of Dendrobium'Sonia'.These compounds were classified into ten pairs of enantiomers or diastereoisomers via chiral resolution,and their structures were determined based on extensive spectroscopic data.Their absolute configurations were determined by hydrolysis,comparison of experimental and calculated electronic circular dichroism(ECD)data,and single-crystal X-ray diffraction analysis.The isolates were evaluated for their ability to inhibit nitric oxide(NO)production in RAW264.7 cells.Among them,syringaresinol(5)exhibited prominent inhibition activity,with an IC50 value of 28.4±3.0μmol·L~(-1),and there was a slight difference between 5a,5b and the racemic mixture 5.
基金supported by National Natural Science Foundation of China(81891012,U19A2010,81630101)Sichuan Province Science and Technology Support Program(2021JDRC0041)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202209).
文摘As a traditional Chinese herbal medicine,Schisandrae Chinensis Fructus(SC)has been used in medicine and food industry due to its health care and therapeutic effects.Over the past 20 years,the use of SC and its active ingredient lignans in the prevention and treatment of liver diseases has been increasing,and their hepatoprotective effects has increased the interest of the public and academia.Therefore,in the present work,we first determined the effectiveness of SC in the treatment of liver diseases such as metabolic associated fatty liver disease,alcoholic liver disease,cholestatic liver disease and acute liver injury.Subsequently,the pharmacological effects and molecular mechanisms of lignans,the active components of SC,for liver disease treatment were comprehensively summarized for the first time.The results showed that the lignans in SC could achieve hepatoprotective effects by regulating lipid metabolism,anti-fibrosis,anti-inflammation,anti-oxidation,anti-tumor and regulating bile acid metabolism.The mechanism mainly involved adenosine 5’-monophosphate-activated protein kinase,endoplasmic reticulum stress,sterol regulatory element binding protein 1c,autophagy,transforming growth factor-β,mitogen-activated protein kinase,microRNA,nuclear factor kappa-B,nuclear factor erythroid-2-related factor 2,heat shock proteins and pregnane X receptor signaling pathways.These results can lay a scientific foundation for the development of hepatoprotective drugs or functional foods from SC/lignans.
基金supported by Project XWZY-2023-0303 supported by Traditional Chinese Medicine Foundation of Xiamen.
文摘In this study,two new kaurane diterpenes(16,17),together with 12 lignans(1-12),a triterpene(15),and two other compounds(13,14)were isolated from the woods of Agathis dammara.The structure of the new compound was determined by HR ESIMS and 1D/2D NMR spectroscopy,and its absolute configuration was determined by electronic circular dichroism(ECD)exciton chirality method.Compounds 5,11,14 exhibit significant hypoglycaemic activity in zebrafish,and their mechanism of action is to enhance glucose uptake in zebrafish.
文摘The identification of natural, plant-derived compounds with pesticidal properties is crucial for developing environmentally sustainable alternatives to synthetic pesticides. In this study, four major lignans—dihydroclusin, cubebin, clusin, and yatein—were isolated from the crude extract of Piper cubeba fruit. Phytotoxicity assays revealed herbicidal activity against Agrostis stolonifera, with dihydroclusin and clusin exhibiting the highest efficacy, inhibiting seed germination by 50% and showing IC50 values of 2.9 µM and 45 µM, respectively, against Lemna paucicostata. Additionally, all compounds, except dihydroclusin, demonstrated fungicidal activity against the strawberry anthracnose pathogen Colletotrichum fragariae. Moreover, only dihydroclusin exhibited larvicidal activity against Aedes aegypti, causing 96% mortality of mosquito larvae at the 100-ppm concentration tested. These findings highlight the broad-spectrum bioactivity of Piper cubeba lignans, suggesting their potential as alternative agents of synthetic pesticides for managing agricultural pests.
文摘To study the antioxidant constituents from the stems of Dendrobium nobile, and to discuss theft structure-activity relationship. Compounds were isolated from a 60% ethanolic extract by various chromatographic techniques and were identified by spectral analysis. The antioxidant activities of compounds were evaluated by DPPH free radical scavenging assay. Five phenanthrenes and four lignans were obtained from the active fractions ofD. nobile. Their structures were identified as fimbriatone （1）, confusarin （2）, flavanthrinin （3）, 2,5-dihydroxy-4,9-dimethoxyphenanthrene （4）, 3,7-dihydroxy-2,4-dimethoxyphenanthrene （5）, syringaresinol （6）, pinoresinol （7）, medioresinol （8） and lirioresinol-A （9）, respectively. Compounds 2 and 6 exhibited more potent DPPH scavenging activities than vitamin C. All the above compounds were reported from this plant for the first time, and compounds 3, 4 and 9 were reported for the first time from the genus of Dendrobiurn. For all phenanthrenes and lignans, an electron-donating methoxyl group in the ortho position to the phenolic hydroxyl group exhibits enhanced antioxidant activities.
文摘A new lignan glycoside, named （7S,8R,8＇R）-（-）-lariciresinol-9-O-a-L-rhamnopyranosyl （1-2） 13-D-glucopyranoside （1）,was isolated from the ethanol extract ofPilea cavaleriei Levi subsp, cavaleriei, together with 17 known lignans （2-18）. The structuresof these compounds were elucidated by extensive spectroscopic analysis, including 1D NMR, 2D NMR and HR-ESI-MS.All the compounds were obtained from the genus Pilea for the first time.
基金This project was supported by National Natural Science Foundation of China.
文摘Seven known dibenzocyclooctadiene lignans,tigloylgomisin P(1), angeloylgomisin P(2),gomisin A(3),Schizandrin(4),angeloylgomisin H(5),gomisin B(6) and R(+)-gomisin M_1(7)were isolated from Kadsura heteroclita.The conformation of tiglolylgomisin P(1)was established by 2D NMR techniques.Using[~3H]platelet activating factor(PAF)binding to human platelet membrane assay,(1),(2)and(7)showed PAF receptor antagonistic activities.
基金financially supported by CAMS Initiative for Innovative Medicine(No.CAMS-2016-I2M-1-010)the Drug Innovation Major Project(No.2018ZX09711001-001-003)。
文摘Four new seco-dibenzocyclooctadiene lignans,kadlongilignans A-D(1-4),consisting of a rare 6,7-seco-(1),two 15,16-seco-(2 and 3) and a 9,10-seco-dibenzocyclooctadiene(4) lignans,were isolated from the roots of Kadsura longipedunculata.Their structures were elucidated by spectroscopic analysis,including extensive NM R,MS and ECD(electronic circular dichroism) spectra.Compounds 3 and 4 exhibited potent inhibitory activities against NO(nitric oxide) production of LPS(lipopolysaccharide)-induced murine macrophages with the inhibition rates of 36.3% and 26.9%,respectively.
基金supported by the National Natural Science Foundation of China (39970534)
文摘This study was aimed to determine whether flaxseed lignans could affect the growth of skeletal muscle in male animals and its possible mechanisms. The impact of flaxseed lignans on the skeletal muscle in male rats was determined in vivo. Flaxseed lignans （50 ppm） and daidzein （5 ppm） were added into the basal diets, respectively. The concentrations of serum lignans and daidzein were measured by high performance liquid chromatography （HPLC）, and the serum growth hormone and testosterone （T） levels were analyzed by radioimmunoassay （RIA）, and the expression of estrogen receptor β （ER β） in the soleus muscle and hypothalamus were determined by reverse-transcription polymerase chain reaction （RT-PCR）. Flaxseed lignans and daidzein could significantly improve the feed efficiency and facilitate the weight gain of the femoral muscle in male rats. The ratio of RNA to DNA in the muscles and serum T levels was remarkably increased, whereas, the urea nitrogen concentrations were significantly decreased by flaxseed lignan and/or its metabolites and daidzein. Meanwhile, the expression of ER β in soleus muscle and hypothalamus were both upgraded by the two phytoestrogens. Flaxseed lignan promoted the growth of male rats, and it might be by regulating serum T levels by binding to ER β in the hypothalamus. In turn, it depressed the catabolism of protein and promoted the hypertrophy of skeletal muscle ceils.
基金National Natural Science Foundation of China(Grant No.81373294)National Key Technology R&D Program"New Drug Innovation"of China(Grant No.2018ZX09711001-008-003)
文摘A phytochemical investigation on the aerial parts of Artemisia brachyloba led to the isolation of 13 compounds（1-13） for the first time, including eight lignans（1-8） and five flavonoids（9-13）. The structures of the isolated compounds were elucidated by analysis of the NMR spectroscopic data and comparison with the literature. The 1 H and 13 C NMR data of 1 were fully assigned for the first time by the 2 D NMR analysis. All the isolates were evaluated for their inhibitory effects on nitric oxide production in lipopolysaccharide-challenged BV-2 microglial cells.
基金the Ministry of Science and Technology of China(2005DKA21006)the Knowledge Innovation Project of Chinese Academy of Sciences.
文摘A new sesquilignan, 7＇,8＇-didehydroherpetotriol （1）, and a new lignan glycoside, （＋）-isolariciresinol-9＇-O-α-L-rhamnopyra- nosy1-（1→6）-[3-D-glucopyranoside （2）, were isolated from the branches of Dipteronia dyeriana. Their structures were elucidated by spectroscopic methods and chemical evidence. Compound 1 possessed inhibitory activity against human leukaemia K562 cells with an IC50 value of 39 μmol/L.
基金supported by the National Key New Drugs Innovation Foundation(No.2015ZX09101025)the National Science Foundation of China(No.81503169)the New Drugs Development Special Foundation of Beijing City of China(No.Z141100002214007)
文摘Herpetospermum caudigerum lignans(HTL),one of the potential drugs with anti-hepatitis B virus and hepatoprotective effects,has limited clinical applications because of poor aqueous solubility and low bioavailability.Both herpetrione(HPE)and herpetin(HPN)are the most abundant ingredients in HTL and exhibit weak acidity.The purpose of the present study was to produce dried preparations of HTL(composed of HPE and HPN)nanosuspensions(HTL-NS)with high redispersibility using lyophilization technology.The HTL-NS was prepared by utilizing precipitation-combined homogenization technology based on acid-base neutralization reactions,and critical formulation and process parameters affecting the characteristics of HTL-NS were optimized.The resultant products were characterized by particle size analysis,SEM,XRD,stability,solubility,dissolution and in vivo bioavailability.HTL-NS showed near-spherical-shaped morphology and the size was 243 nm with a narrow PDI value of 0.187.The dried preparations with a relatively large particle size of 286 nm and a PDI of 0.215 were achieved by using 4%(W/V)mannitol as cryoprotectants,and had a better stability at 4 or 25 oC for 2 months,compared to HTL-NS.In the in vitro test,the dried preparations showed markedly increased solubility and dissolution velocity.Besides,in the in vivo evaluation,it exhibited significant increases in AUC0–t,C_(max),MRT and a decrease in T_(max),compared to the raw drug..In conclusion,our results provide a basis for the development of a drug delivery system for poorly water-soluble ingredients with p H-dependent solubility.
基金financially supported by the National Key New Drugs Innovation Foundation(No.2016X09101073)the National Natural Science Foundation of China(No.81573697)
文摘The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills(GNDP) by transforming lignans of Herpetospermum caudigerum(HL) composed of herpetrione(HPE) and herpetin(HPN) into nanosuspension(HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles(HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015 J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy(PCS), zeta potential measurement, and scanning electron microscopy(SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC0–t, Cmax and decrease in Tmax when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.
基金supported by the Research Grants Council of the Hong Kong Special Administrative Region,China(Nos.HKBU12103618 and HKBU12103917)the Research Grants Council of the Hong Kong Baptist University(HKBU)+2 种基金Interdisciplinary Research Matching Scheme(No.RC-IRMS/15-16/02)the Hong Kong Scholars Program Foundation(No.XJ2015047)Mr.Kwok Yat Wai and Madam Kwok Chung Bo Fun Graduate School Development Fund(WANG Dong-Ying)
文摘Twenty-one lignans including three new ones(1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1 D and 2 D NMR analysis. These compounds were evaluated for their cytotoxic and anti-HIV activities. The new secoisolariciresinol dimethyl ether acetate(13) exhibited anti-HIV-1 activity with an IC50 value of 5.27 μmol·L^-1 and a selective index(SI) value of 2.2. The known arylnaphthalene lignan procumbenoside A(3) and diphyllin(8) demonstrated inhibitory activity against HIV-1 with IC50 values of 4.95(SI > 6.2) and 0.38 μmol·L^-1(SI = 5.3), respectively.
基金supported by the National Science Fund for Distinguished Young Scholars(81525026)Shenzhen Government’s Plan of Science and Technology(JCYJ20170412110504956).
文摘Ten neolignans or norlignans(1-10)including eight new compounds were isolated from the whole bodies of Polyphaga plancyi Bolivar.Their structures were identified by spectroscopic data.Compounds 3,4,8,and 9 are racemates indicated by chiral HPLC analysis.Chiral separation followed by ECD calculations allowed to clarify the absolute configurations of all the antipodes.All the new compounds were evaluated for their biological properties toward extracellular matrix in rat renal proximal tubular cells,human cancer cells(K562,A549,and Huh7),EV71,ROCK2,JAK3,DDR1,and coagulation.
