Lignans are the main active components of Schisandrae Chinensis Fructus for liver disease treatment:a review

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.

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.

Antioxidant phenanthrenes and lignans from Dendrobium nobile

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.

Herpetin, a New Bioactive Lignan Isolated from Herpetospermum caudigerum

Aim To study the chemical constituents of seeds of Herpetospermum caudigerum. Methods Column chromatography was used in the isolation procedure, and the structure was elucidated by spectral data, whose pharmacologic activity was assayed in vitro. Results A new compound named herpetin was isolated, whose structure was determined to be 3-benzofuran methanol-2, 3-dihydm-2-（4- hydroxy-3-methoxyphenyl ）-4-methoxy-6-[ tetrahydm-2-（ 3-hydroxy-4-methoxyphenyl ）-3-methanol ]-2- furanmethyl, showed significant inhibitory effects on HBV-DNA and the replication and expression of HBsAg and HBeAg. Conclusion Herpetin offers wide research and development prospect.

A New Lignan from Isodon lophanthoides var. gerardianus (Labiatae)

A new lignan, together with a known one, was isolated from Isodon lophanthoides var. gerardianus [Bentham] H. Hara. The structure of the new lignan was elucidated as 1_acetoxyl_2e_piperonyl_6e_[6_methoxyl_piperonyl]_3,7_dioxabicyclo_[3,3,0]_octane mainly by 1D and 2D NMR techniques.

Dibenzocyclooctadiene Lignans with Platelet-Activating Factor (PAF) Antagonist Activity from Kadsura heteroclita

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.

A new lignan derivative from the root of Ilex pubescens

One new compound, ilexlignan A （1）, was isolated from the root of llex pubescens. Its structure was elucidated by the combination of one- and two-dimensional NMR analysis, mass spectrometry, CD spectrum measurement and chemical evidence.

Flaxseed Lignans Promoted the Growth of Skeletal Muscle in Male Rats and Its Possible Mechanism

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.

Two new lignans from Dipteronia dyeriana

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.

A new lignan from Gynostemma pentaphyllum

A new lignan ligballinone 1 with the know ligbaUinol 2 were isolated from plant Gynostemma pentaphyllum. Their structures were determined through spectroscopic methods including ESI-MS, 1D and 2D NMR （^1H, ^13C, DEPT, ^1H-^1H COSY, HMQC, HMBC） and X-ray diffraction experiment for 2.

Two new benzofuran lignan glycosides from Gelsemium elegans

Two new benzofuran lignan glycosides, gelsemiunoside A and B, were isolated from the whole plant of Gelsemium elegans Benth. Their structures were elucidated on the basis of spectroscopic evidence. Furthermore, gelsemiunoside A and B were shown a potent cytotoxic activity by suppressing the proliferation of A375-S2 cells.

New lignan glycosides from Glehnia littoralis

From the roots ethanol extract of Glehnia littoralis, two new lignan glycosides, named glehlinoside E （1） and F （2）, were obtained. Their structures were determined to be （-）-secoisolariciresinol 4-O-β-D-（6-O-feruloyl） glucopyranoside （1） and （-）- secoisolariciresinol 4-O-f-β-D-（6-O-caffeloyl） glucopyranoside （2） by analysis of their spectral data, respectively.

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 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.

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.

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.

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.

Microwave assisted-semi bionic extraction of lignan compounds from Fructus Forsythiae by orthogonal design

Microwave assisted-semi bionic extraction (MASBE) process for lignans from Fructus Forsythiae was studied. The influences of solvent pH value, microwave power, dosage of solvent and irradiation time were investigated. Optimum extracting parameters were determined by orthogonal experiments as follows: pH value of solvent at first extraction is 5.5-6.0, that at the second extraction is 7-8; microwave power is 700 W; mass ratio of Fructus Forsythiae to water is 1-12; irradiation time is 10 min, and extracting times is two. Under these optimal conditions, the yield of lignans reaches 0.364%. Compared with the conventional extraction methods, the MASBE process has the advantages of high extraction rate, high extraction selectivity.

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.