Antioxidant lignans sesamin and sesamolin in sesame(Sesamum indicum L.):a comprehensive review and future prospects

Sesame(Sesamum indicum L.)is a significantly lucrative cash crop for millions of small-holder farmers.Its seeds are an important source of a highly appreciated vegetable oil globally and two clinically essential antioxidant lignans,sesamin and sesamolin.Accordingly,many countries import millions of tons of sesame seed every year.The demand for lignan-rich sesame seeds has been increasing in recent years due to the continuous discovery of several pharmacological attributes of sesamin and sesamolin.To meet this demand,the sesame breeder’s primary objective is to release sesame cultivars that are enriched in oil and lignans.Thus,it is necessary to summarize the information related to the sesamin and sesamolin contents in sesame in order to promote the joint efforts of specialized research teams on this important oilseed crop.In this article,we present the current knowledge on the sesamin and sesamolin contents in S.indicum L.with respect to the updated biosynthesis pathway,associated markers,governing loci,available variability in sesame germplasm,the in planta potential roles of these compounds in sesame,and the newly discovered pharmacological attributes.In addition,we propose and discuss some required studies that might facilitate genomics-assisted breeding of high lignan content sesame varieties.

Exploring a novel class tryptophan hydroxylase 1 inhibitor derived from Sambucus williamsii Hance for the osteoporosis treatment

Objective:Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation.Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance,a folk herbal medicine used to treat bone fractures and joint diseases in China,exerted bone-protective effects,and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1(TPH-1).However,there is no direct evidence for the action of lignans on TPH-1.This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties.Methods:Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1.The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells.The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined.Result:The lignans showed high binding scores and binding affinities to TPH-1,inhibited the activity and protein expression of TPH-1,suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density.Conclusion:This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases,including osteoporosis.

Neolignans and Norlignans from Insect Medicine Polyphaga plancyi and Their Biological Activities

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.

Neolignans from Selaginella moellendorffii

Two new neolignans selaginellol(1)and selaginellol 4'-O-β-D-glucopyranoside(2),together with seven known compounds(3–9),were isolated from the whole plant of Selaginella moellendorffii.The structures of the new isolates were determined through spectroscopic data analysis.Compounds 1–9,as well as compounds 10–18 previously isolated from the species,were measured for the activity against platelet aggregation induced by ADP or collagen.Three neoligans(8,11,and 12),one flavanone(14),and one alkaloid(16)showed inhibitory activity against ADP-or collagen-induced platelet aggregation as compared with tirofiban.The dihydrobenzofuran neolignans(8,11,and 12)are more potent than the benzofuran neolignan(13)and other types of neolignans(1–7).Glucosidation of the dihydrobenzofuran neolignans(11 and 12)is helpful for the activity.Graphical Abstract Two new neolignans selaginellol(1)and selaginellol 40-O-b-D-glucopyranoside(2)were isolated from the whole plant of Selaginella moellendorffii.Several compounds from this plant showed the activity against platelet aggregation induced by ADP or collagen.

Highly Oxygenated Limonoids and Lignans from Phyllanthus flexuosus

Two new highly oxygenated limonoids,flexuosoids A(1)and B(2),and three new arylnaphthalene lignan glycosides,phyllanthusmins D–F(3–5),were isolated from the roots of Phyllanthus flexuosus,in addition to three known lignans,phyllanthusmin C,arabelline,and(?)-diasyringaresinol.Their structures were elucidated on the basis of detailed spectroscopic analysis and chemical methods.Compounds 1 and 2,two new decaoxygenated limonoids with a C-19/29 lactol bridge and heptaoxygenated substituents at C-1,C-2,C-3,C-7,C-11,C-17,and C-30,represent the second example of limonoids in the Euphorbiaceae family.Most of the isolates were tested for their antifeedant,anti-herpes simplex virus 1,and cytotoxic activities.The new limonoids 1 and 2 showed promising antifeedant activity against the beet army worm(Spodoptera exigua)with EC50 values of 25.1 and 17.3 lg/cm2,respectively.In addition,both of them displayed moderate cytotoxicity against the ECA109 human esophagus cancer cell line,along with the known lignan glycoside,phyllanthusmin C,with the IC50 values of 11.5(1),8.5(2),and 7.8(phyllanthusmin C)lM,respectively.

Lignans from Seeds of Herpetospermum caudigerum Wall.Protect Against Alcoholic Liver Injury via TGF-β/Smads Pathway in Rats

[Objectives]This study aimed to investigate the effects of lignans from seeds of Herpetospermum caudigerum Wall.(SHC)on expression of TGF-β/Smads in liver tissue of hepatic alcohol-injuried rats,and to explore its protective mechanism.[Methods]A total of 60 SD rats were randomly divided into six groups.The rats in all the groups except those in the normal group were given with white spirit by gavage for 8 weeks to establish alcoholic liver injury models.After rat models were established successfully,they were administered intragastrically with 400,200 and 100 mg/kg of lignans,respectively.The rats in the normal group were administered intragastrically with 50 mg/kg of silymarin.The administration lasted for 8 weeks,once a day.The changes in the general state,liver tissue pathology and collagen deposition of the rats were observed.The expression of TGF-β,TGF-β1 receptor 1(TβR-I),TGF-β1 receptor 2(TβR-II),Smad2/p-Smad2 and Smad3/p-Smad3 in the hepatic tissue was detected.[Results]The expression levels of TGF-β1,Smad2,p-Smad2,and p-Smad3 significantly declined,and the expression levels of TβR-I,TβR-II and Smad3 did not change significantly in the liver tissue of rats in the lignans groups and the expression levels of TGF-β,Smad2,and p-Smad3 significantly declined.Meanwhile,the expression levels of TβR-I,TβR-II,p-Smad2 and Smad3 did not change significantly in the silymarin group.[Conclusions]The lignans from SHC have significant intervention effects on alcoholic livery injury.The mechanism may be related to the inhibition of hepatic stellate cell(HSC)activation,TGF-βsecretion and p-Smad2,p-Smad3 expression in the signaling pathway.

Four new lignans from the leaves and stems of Schisandra propinqua var.sinensis

Four new tetrahydrofuran lignans,schpropinrins A-D(1-4),together with five known ones,were isolated from the leaves and stems of Schisandra propinqua var.sinensis.Their structures,including absolute configurations,were characterized by means of spectroscopic analysis and ECD calculation.Compounds 1-4 featured a ketal or hemiketal substructure at C-7 and all of the isolates were tested for their anti-HIV integrase activity.

STUDIES ON SEPARATION AND DETERMIINATION OF THE LIGNANS IN DIPHYLLEIA SIENSIS LI BY RP-HPLC

A simple,sensitive and accurate RP-HPLC method for the separation anddetermination of eight lignans in Diphylleia sinensis was described.The methodhas been applied to the analysis of different samples.

Lignans and sesquiterpenoids from the stems of Schisandra bicolor var. tuberculata

A pair of new tetrahydrofuran lignan enantiomers,(±)-schibiculatin A[(±)-1],a new enedione lignan,schibiculatin B(2),two new cadinane-type sesquiterpenoids,schibiculatins C(3)and D(4),along with two known seco-cadinane-type sesquiterpenoids(5 and 6)and seven known miscellaneous lignans(7-13)were isolated from the stems of Schisandra bicolor var.tuberculata.The structures of 1-4 were elucidated by comprehensive analysis of their spectro-scopic data,quantum chemical calculations,as well as single-crystal X-ray diffraction.A few isolated compounds were tested for their protective activities against corticosterone-induced apoptosis in PC12 cells.Among them,compounds 5 and 6 showed moderate activities.

Studies on the Synthesis of Sesamin-Group Lignans Ⅷ. A Simplified Sythesis of 2-Aryl-4-phenyloxazoles and 2-Alkyl-4-phenyloxazoles

The reaction of phenacyl benzoate derivatives with acetamide at about 140°in the presence of BF3 catalyst gave 2-aryl-4-phenyloxazoles. This method can be applied to the preparation of 2-alkyl-4-phenyloxazoles as well.

Isolation and characterization of lignans from the leaves of Isatis indigotica Fortune

A phytochemical investigation of 80%EtOH exact of Isatis indigotica Fortune leaves yielded ten lignans(1-10),including six furofurans lignans(1-6),one arylnaphthalenes lignans(7)and three tetrahydrofurans lignans(8-10).Their structures were determined by HRESIMS spectroscopic data and extensive NMR analyses.Among them,compounds 6,9 and 10 were isolated from the genus oi Isatis for the first time.

Research progress on the lignans from the genus Schisandra and their biological activities

The plants of the genus Schisandra belong to the Schisandraceae family.As one of the main active components of genus Schisandra,lignans have rich biological activities,including anti-inflammatory,anti-tumor,anti-HIV and PAF antagonism.This article summarizes and classifies the types and activities of lignans isolated from the genus Schisandra in the past ten years.

The ERF transcription factor LTF1 activates DIR1 to control stereoselective synthesis of antiviral lignans and stress defense in Isatis indigotica roots

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health.Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement.Here,we identified the complete pathway to stereoselectively synthesize antiviral(-)-lariciresinol glucosides in Isatis indigotica roots,which consists of three-step sequential stereoselective enzymes DIR1/2,PLR,and UGT71B2.DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content.Mechanistically,the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1.These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize(-)-lariciresinol derived antiviral lignans in I.indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses.In conclusion,the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

Research progress and quality markers prediction analysis of Dysosma versipellis

Dysosma versipellis is the rhizome of Bajiaolian in Berberaceae.It is a unique medicinal plant in China and it was the first to be recorded in Shennong’s Classic of Materia Medica(unknown author,25–220 C.E.).It has complex chemical components as well as complex,pharmacological and toxicological effects are extensive.Based on the recent research progress,the chemical constituents,pharmacological activities and toxicological effects of Dysosma versipellis were summarized.Combined with the core concept of quality markers of traditional Chinese medicine,the prediction and analysis were carried out from the aspects of phytogenetics and the source pathway of specific chemical constituents,traditional medicinal properties,traditional efficacy,chemical composition measurability,blood components,and pharmacokinetics,in order to provide reference for further study of Dysosma versipellis.

First Enantioselective Synthesis of (2R,3R)-and(2S,3S)-2-(4-hydroxyphenyl)-3-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde

A novel enantioselective synthetic approach to 1,4-benzodioxane lignans was reported in which (2R, 3R)- and (2S, 3S)-2-(4-hydroxyphenyl)-3-hydroxymethyl-1, 4-benzodioxan-6-carbaldehyde were first synthesized.

Dimethylfuroguaiacin的全合成研究

Lignans是近年来天然产物中研究较为活跃的领域之一,丰富的结构类型和显著的生理活性受到人们的广泛关注。在众多结构的Lignans中,呋喃型木脂素在天然产物中存量较少,相继发表的综述也未提及,因而成为被遗忘的研究领域。 1

Diterpenoid Alkaloids and One Lignan from the Roots of Aconitum pendulum Busch

Diterpenoid alkaloids have neroprotective activity.Herein,three napelline-type diterpenoid alkaloids 1-3,two aconitine-type diterpenoid alkaloids 4-5,and one isoquinline-type alkaloid 6,as well as one lignan glycoside 7,have been isolated from the roots of Aconitum pendulum Busch.Compounds 1 and 7 were new compounds,and their chemical structures were determined on the basis of nuclear magnetic resonance(NMR)spectra and mass spectrometry analysis.A ThT assay revealed that compound 2 showed significant disaggregation potency on the Aβ_(1−42)aggregates.

Two New Compounds from Schisandra propinqua var.propinqua

Schisanpropinoic acid(1),a new bergamotane sesquiterpenoid,and schisanpropinin(2),a new tetrahydrofuran lignan with a rare epoxyethane unit,were identified from the stems and leaves of Schisandra propinqua var.propinqua.Their structures were determined based on comprehensive spectroscopic and mass spectrometric analysis.The absolute configuration of 1 was determined by X-ray analysis.Compounds 1 and 2 were tested for their cytotoxic activity against five human tumor cell lines.

Two New Arylnaphthalene Lignan Glycosides from Mananthes patentiflora

Two new diphyllin glycosides, mananthoside A (1) and B (2), together with six known compounds, were isolated from the ethanolic extract of the whole plants of Mananthes patentiflora. Their structures were determined on the basis of chemical and spectral evidences.

Chemical constituents, cytotoxic, antifungal and antimicrobial properties of Centaurea diluta Ait. subsp. algeriensis(Coss. & Dur.) Maire

Objective:To investigate the chemical composition of a moderately polar extract(CHC1_3 soluble part of the MeOH-H_2O extract) obtained from the aerial parts(leaves and flowers) of Centaurea diluta Ait.subsp.algeriensis(Coss.& Dur.) Maire,a species endemic to Algeria and Morocco on which no reports are available to date.To evaluate in vitro the cytotoxic,antifungal and antimicrobial activities of this extract and the cytotoxic and antimicrobial activities of its isolated secondary metabolites.Methods:The cytotoxic effects of the extract were investigated on 3 human cancer cell lines i.e.the A549 non-small-cell lung carcinoma(NSCLC),the MCF7 breast adenocarcinoma and the U373 glioblastoma using a MTT colorimetric assay.Biological data allowed to guide the fractionation of the extract by separation and purification on silica gel 60(CC and TLC).The isolated compounds which were characterized by spectral analysis,mainly HR-ESIMS,HR-EIMS,UV and NMR experiments(~1H,^(13)C,COSY,ROESY,HSQC and HMBC) and comparison of their spectroscopic data with those reported in the literature,were evaluated for cytotoxic activities on six cancer cell lines(A549,MCF7,U373,Hs683 human glioma,PC3 human prostate and B16-F10 murine melanoma).The direct and indirect antibacterial and antifungal activities were determined using microdilution methods for the raw extract and TLC-bioautography and microdilution methods against standard and clinical strains for the isolated compounds.Results:The raw extract reduced cell viability with IC_(50)s of 27,25 and 21 μg/mL on A549,MCF7 and U373,respectively.Five secondary metabolites:two phenolic compounds(vanillin 1,paridol 3),a lignan[(-)-arctigenin 2]and two flavonoid aglycones(eupatilin 4 and jaceosidin 5),were then isolated from this extract.Moderate cytotoxic effects were observed for(-)-arctigenin 2(IC_(50)s:28 and 33μM on Hs683 and B16-F10,respectively),eupatilin 4(IC_(50)s:33 and 47 μM on B16-F10 and PC3,respectively) and jaceosidin 5(IC_(50)s:32 and 40 μM on PC3 and B16-F10,respectively).Conclusions:All the isolated compounds were described for the first time from this species.Although inactive against 7 tested microorganisms(fungi,bacteria and yeast,human or plant pathogens),the raw extract was able to potentiate the effect of beta-lactam antibiotics on methicillin-resistant Staphylococcus aureus(MRSA),reducing the minimal inhibitory concentrations(MICs) by a factor of 2-32-fold.No synergy was found between the extract and streptomycin.From the five isolated compounds only jaseosidin 5 showed a moderate antimicrobial activity.