Dibenzylbutyrolactone Lignan Research Articles

Anthriscus sylvestris Deoxypodophyllotoxin Synthase Involved inthe Podophyllotoxin Biosynthesis.

Tetrahydrofuran ring formation from dibenzylbutyrolactone lignans is a key step in the biosynthesis of aryltetralin lignans including deoxypodophyllotoxin and podophyllotoxin. Previously, Fe(II)- and 2-oxoglutarate-dependent dioxygenase (2-ODD) from Podophyllum hexandrum (Himalayan mayapple, Berberidaceae) was found to catalyze the cyclization of a dibenzylbutyrolactone lignan, yatein, to give deoxypodophyllotoxin and designated as deoxypodophyllotoxin synthase (DPS). Recently, we reported that the biosynthesis of deoxypodophyllotoxin and podophyllotoxin evolved in a lineage-specific manner in phylogenetically unrelated plant species such as P. hexandrum and Anthriscus sylvestris (cow parsley, Apiaceae). Therefore, a comprehensive understanding of the characteristics of DPSs that catalyze the cyclization of yatein to deoxypodophyllotoxin in various plant species is important. However, for plant species other than P. hexandrum, the isolation of the DPS enzyme gene and the type of the enzyme, e.g.whether it is 2-ODD or another type of enzyme such as cytochrome P-450, have not been reported. In this study, we report the identification and characterization of A. sylvestris DPS (AsDPS). Phylogenetic analysis showed that AsDPS belonged to the 2-ODD superfamily and shared moderate amino acid sequence identity (40.8%) with P. hexandrum deoxypodophyllotoxin synthase (PhDPS). Recombinant protein assay indicated that AsDPS and PhDPS differ in terms of the selectivity of substrate enantiomers. Protein modeling using AlphaFold2 and site-directed mutagenesis indicated that the Tyr305 residue of AsDPS probably contributes to substrate recognition. This study advances our understanding of the podophyllotoxin biosynthetic pathway in A. sylvestris and provides new insight into 2-ODD involved in plant secondary (specialized) metabolism.

Synthesis and Anti-Proliferative Evaluation of Arctigenin Analogues with C-9' Derivatisation.

Dibenzylbutyrolactone lignans (DBLs) are a class of natural products with a wide variety of biological activities. Due to their potential for the development of human therapeutic agents, DBLs have been subjected to various SAR studies in order to optimise activity. Previous reports have mainly considered changes on the aromatic rings and at the benzylic carbons of the compounds, whilst the effects of substituents in the lactone, at the C-9' position, have been relatively unexplored. This position has an unexploited potential for the development of novel dibenzyl butyrolactone derivatives, with previous preliminary findings revealing C-9'-hydroxymethyl analogues inducing programmed cell cycle death. Using the core structure of the bioactive natural product arctigenin, C-9' derivatives were synthesised using various synthetic pathways and with prepared derivatives providing more potent anti-proliferative activity than the C-9'-hydroxymethyl lead compound.

Organocatalytic aldol approach for the protecting group-free asymmetric synthesis of (7R')-parabenzlactone, (-)-hinokinin, (-)-yatein, (-)-bursehernin, (-)-pluviatolide, (+)-isostegane and allied lignans.

A short and efficient catalytic asymmetric protection-free synthesis of dibenzylbutyrolactone lignans, such as (-)-hinokinin, (-)-yatein, (-)-bursehernin, (-)-pluviatolide, and their 7'-hydroxylignans - (7'R)-parabenzlactone, (7'R)-hydroxyyatein, (7'R)-hydroxybursehernin, and (7'R)-hydroxy pluviatolide, respectively, is described. The syntheses of (+)-isostegane and the formal synthesis of (-)-podophyllotoxin and bicubebins are also described. Organocatalytic aldol-reduction-lactonization and Pd/C-catalyzed hydrogenative debromination are two-pot sequential reactions for the enantioselective synthesis of hydroxybutyrolactone 13b with excellent diastereo- and enantioselectivity (dr 33 : 1 and >99% ee). The protecting group-free chemoselective α-alkylation of 13b directly led to 7'-hydroxydibenzylbutyrolactone lignans, followed by hydrogenative dehydroxylation, which led to their (deoxy) dibenzylbutyrolactone lignans, and the syntheses were completed in three to five steps from 6-bromopiperonal.

Serial five-membered lactone ring ions in the treatment of Alzheimer's diseases-comprehensive profiling of arctigenin metabolites and network analysis.

Arctigenin is a phenylpropanoid dibenzylbutyro lactone lignan compound with multiple biological functions. Previous studies have shown that arctigenin have neuroprotective effects in Alzheimer's disease (AD) models both in vivo and in vitro; however, its metabolism in vivo has not been studied. Most traditional analytical methods only partially characterize drug metabolite prototypes, so there is an urgent need for a research strategy that can fully characterize drug metabolites. In the present study, ions fishing with a serial five-membered lactone ring as a fishhook strategy based on ultrahigh-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was utilised to characterise the metabolism of arctigenin, and the establishment of this strategy also solved the challenge of creating a comprehensive metabolic profile of neolignan. Based on the proposed strategy, a total of 105 metabolites were detected and characterised, 76 metabolites of which were found in rats and 49 metabolites in liver microsomes. These metabolites were postulated to be produced through oxidation, reduction, hydrolysis, and complex reactions. Subsequently, network pharmacology was utilized to elucidate the mechanism of arctigenin and its main metabolites against Alzheimer's disease, screening 381 potential targets and 20 major signaling pathways. The study on the comprehensive metabolism of arctigenin provides a holistic metabolic profile, which will help to better understand the mechanism of arctigenin in the treatment of Alzheimer's disease (AD) and also provide a basis for the safe administration of arctigenin.

Flavonols, lignans and diacetylenes from leaves of Hydrocotyle leucocephala Cham. & Schltdl. and aerial parts of H. bonariensis Comm. ex Lam

Chemical investigation of ethyl acetate and n-butanol fractions from methanol extracts from leaves of Hydrocotyle leucocephala Cham. & Schltdl. and aerial parts of H. bonariensis Comm. ex Lam. resulted in the identification of 6 compounds and a putative identification of 12 more, including thirteen glycosylated flavonols (1–13), two dibenzylbutyrolactone lignans (14 and 15) and three diacetylenes (16–18) based on UPLC-ESI-QToF-MS/MS analysis in the positive and negative ionization modes. In the case of compounds 3, 14–18, their structures were confirmed by analysis of NMR spectra. Compounds 5, 7, 10–12 or isomeric compounds of them were identified for the first time in this genus. The obtained results contribute with chemotaxonomy of Hydrocotyle since flavonoids, dibenzylbutyrolactone lignans, and diacetylenes were characterized, in consonance with other species previously investigated.

Two O-Methyltransferases from Phylogenetically Unrelated Cow Parsley (Anthriscus sylvestris) and Hinoki-Asunaro (Thujopsis dolabrata var. hondae) as a Signature of Lineage-Specific Evolution in Lignan Biosynthesis.

O-Methyltransferases (OMTs) play important roles in antitumor lignan biosynthesis. To date, six OMTs catalyzing the methylation of dibenzylbutyrolactone lignans as biosynthetic precursors of antitumor lignans have been identified. However, there is still no systematic understanding of the diversity and regularity of the biosynthetic mechanisms among various plant lineages. Herein, we report the characterization of two OMTs from Anthriscus sylvestris and Thujopsis dolabrata var. hondae [designated as AsSecoNorYatein (SNY) OMT and TdSNYOMT] together with the six known OMTs to evaluate their diversity and regularity. Although A. sylvestris 5-O-methylthujaplicatin (SecoNorYatein) and 4-O-demethylyatein (NorYatein) OMT (AsSNYOMT) and TdSNYOMT accept 5-O-methylthujaplicatin and 4-O-demethylyatein as substrates, phylogenetic analysis indicated that these two OMTs shared low amino acid sequence identity, 33.8%, indicating a signature of parallel evolution. The OMTs and the six previously identified OMTs were found to be diverse in terms of their substrate specificity, regioselectivity and amino acid sequence identity, indicating independent evolution in each plant species. Meanwhile, two-entropy analysis detected four amino acid residues as being specifically acquired by dibenzylbutyrolactone lignan OMTs. Site-directed mutation of AsSNYOMT indicated that two of them contributed specifically to 5-O-methylthujaplicatin methylation. The results provide a new example of parallel evolution and the diversity and regularity of OMTs in plant secondary (specialized) metabolism.

Preventive effects of arctigenin from Arctium lappa L against LPS-induced neuroinflammation and cognitive impairments in mice.

Arctigenin (Arc) is a phenylpropanoid dibenzylbutyrolactone lignan in Arctium lappa L, which has been widely applied as a traditional Chinese herbal medicine for treating inflammation. In the present study, we explored the neuroprotective effect and the potential mechanisms of arctigenin against LPS-evoked neuroinflammation, neurodegeneration, and memory impairments in the mice hippocampus. Daily administration of arctigenin (50mg/kg per day, i.g.) for 28days revealed noticeable improvements in spatial learning and memory deficits after exposure to LPS treatment. Arctigenin prevented LPS-induced neuronal/synaptic injury and inhibited the increases in Abeta (Aβ) generation and the levels of amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1). Moreover, arctigenin treatment also suppressed glial activation and reduced the production of proinflammatory cytokines. In LPS-treated BV-2 microglial cells and mice, activation of the TLR4 mediated NF-κB signaling pathway was significantly suppressed by arctigenin administration. Mechanistically, arctigenin reduced the LPS-induced interaction of adiponectin receptor 1 (AdipoR1) with TLR4 and its coreceptor CD14 and inhibited the TLR4-mediated downstream inflammatory response. The outcomes of the current study indicate that arctigenin mitigates LPS-induced apoptotic neurodegeneration, amyloidogenesis and neuroinflammation as well as cognitive impairments, and suggest that arctigenin may be a potential therapeutic candidate for neuroinflammation/neurodegeneration-related diseases.

The enantioselective total syntheses of (+)-7-oxohinokinin, (+)-7-oxoarcitin, (+)-conicaol B and (-)-isopolygamain.

A flexible approach to C7 keto dibenzyl butyrolactone lignans was developed and the synthesis of several natural products and their related derivatives is described herein. The developed pathway proceeds through enantioenriched β-substituted butyrolactones, from which facile aldol addition and subsequent oxidation affords the desired benzylic ketone moiety. This methodology was used to complete the first enantioselective total syntheses of three natural products, (+)-7-oxohinokinin, (+)-7-oxoarcitin and (+)-conicaol B, and a further five analogues. The utility of this method was further demonstrated through a 1-2 step modification to access another class of natural product, aryltetralin lignans, allowing the asymmetric total synthesis of (-)-isopolygamain and a polygamain derivative. Anti-proliferative testing determined (-)-isopolygamain was the most active of the compounds prepared, with IC50 values of 2.95 ± 0.61 μM and 4.65 ± 0.68 μM against MDA-MB-231 (triple negative breast cancer) and HCT-116 (colon cancer) cell lines, respectively.

Effects of dibenzylbutyrolactone lignans arctigenin and trachelogenin on the motility of isolated rat ileum

Dibenzylbutyrolactone-type lignans are phenolic compounds of medical importance. The purpose of the study was to determine the effects of two such lignans, arctigenin and trachelogenin on the motility of isolated rat ileum and obtain indications on their mechanism of action. They were isolated from Arctium lappa and Cirsium arvense, respectively, which have been used traditionally to treat gastrointestinal disorders. 1–1.5 cm long segments of distal ileum were obtained from adult male Wistar rats. The intestinal segments were suspended vertically in a well-aerated organ-bath according to Magnus mounting method. The intestinal motility was monitored for 30 min before treatment to obtain the baseline, followed by treatment with 1 µM, 10 µM, 20 µM and 40 µM concentrations of arctigenin and 0.5 µM, 1 µM, 10 µM and 20 µM of trachelogenin concentrations. The amplitude, tone, and period of spontaneous contractions were measured after 15 and 30 min of treatment. To investigate their mechanism of action, cholinergic, glutamatergic, adrenergic antagonists and compounds inhibiting nitric oxide synthase and L-type calcium channels were also tested. Arctigenin and trachelogenin decreased the frequency of contractions in a dose-dependent manner. At the concentration of 20 µM and 40 µM of trachelogenin and arctigenin, respectively, there was a marked alteration in spontaneous contraction pattern with an observable increase in the period time. This activity was comparable to 0.5 µM nifedipine (L-type calcium channel blocker) treatment. Our results demonstrate relaxant effect of arctigenin and trachelogenin on the ileum motility that may be mediated by L-type calcium ion channel blockade.

WITHDRAWN: Polyphenolic-protein-polysaccharide conjugates from Spica of Prunella vulgaris: Chemical profile and anti-herpes simplex virus activities

Previous studies showed that the water extract (PVW) from Spica of Prunella vulgaris Linn. (Labiatae) exerts anti-herpes simplex virus (HSV) activity. Evaluation the antiviral activity of the graded ethanol precipitations indicated that 30% ethanol precipitate (PVE30) was the active principle of water extract (PVW). Further activity-oriented separation of PVE30 through salting-out method revealed that the anti-HSV activity of P. vulgaris glycoconjugates (PVG) was more potent than PVE30 and PVW, 2-fold and 4-fold, respectively. UPLC-QTOF-MS/MS, FT-IR and NMR techniques identified PVG as a type of polyphenolic-protein-polysaccharides (PPPs) with an average molecular weight of 41.69 kDa. PVG was composed of dibenzylbutyrolactone lignan units, and rich in galacturonic acid, xylose, rhamnose, rhamnose, arabinose, glucose monosaccharide units, glutamic acid and aspartic acid. Further in vitro antiviral testing confirmed that PVG substantially and stably inhibited acyclovir (ACV) resistant HSV strains; its inhibitory action was even better than the positive control ACV. Overall, our findings support PVG as a potential drug resource for anti-HSV therapy.

Simplified Derivatives of Dibenzylbutyrolactone Lignans from Hydrocotyle bonariensis as Antitrypanosomal Candidates.

The search for the pharmacophore of a bioactive compound, crucial for drug discovery studies, involves the adequate arrangement of different atoms in the molecule. As part of a continuous work aiming discovery of new drug candidates against the protozoan parasite Trypanosoma cruzi, the hexane extract of Hydrocotyle bonariensis was subjected to a bioactivity-guided fractionation to afford two chemically related dibenzylbutyrolactone lignans - hinokinin (1) and hibalactone (2). Compounds 1 and 2 showed activity against trypomastigote with EC50 values of 17.0 and 69.4 μM, respectively. Compound 1 was also active against the clinically relevant form of the parasite, amastigotes, displaying an EC50 value of 34.4 μM. The structure-activity relationship (SAR) indicated that the absence of the double bond at C-7 is a crucial feature for the increment of the antiparasitic activity. The lethal action of the most potent compound 1 was investigated in the trypomastigotes. The fluorescent-based assay with SYTOX Green demonstrated a significant alteration of the plasma membrane permeability of the parasite. Additionally, compound 1 demonstrated no significant hemolytic activity in mice erythrocytes at 200 μM. To search the pharmacophore, three different simplified compounds - 3,4-methylenedioxydihydrocinnamic acid (3), 3,4-methylenedioxydihydrocinnamic alcohol (4) and 3,4-methylenedioxycinnamic acid (5) - were prepared and tested against T. cruzi. These derivatives displayed EC50 values of 37.2 (3), 25.8 (4) and 73.5 (5) μM against trypomastigotes, and 41.3 (3) and 48.2 (4) μM against amastigotes, whereas compound 5 was inactive. Except for compound 2, which resulted in a CC50 value of 114.5 μM, all compounds showed no mammalian cytotoxicity at 200 μM. An in silico ADMET study was performed and predicted values demonstrated an acceptable drug-likeness profile for compounds 1-5. Despite the minor reduction in the potency, the simplified derivatives retained the antitrypanosomal activity against the intracellular amastigotes, even with 95 % reduction of their molecular weight. Additionally, in silico studies suggested them as more soluble compounds, making these simplified structures promising scaffolds for optimization studies in Chagas disease.

Plant-derived lignans as potential antiviral agents: a systematic review.

Medicinal plants are one of the most important sources of antiviral agents and lead compounds. Lignans are a large class of natural compounds comprising two phenyl propane units. Many of them have demonstrated biological activities, and some of them have even been developed as therapeutic drugs. In this review, 630 lignans, including those obtained from medicinal plants and their chemical derivatives, were systematically reviewed for their antiviral activity and mechanism of action. The compounds discussed herein were published in articles between 1998 and 2020. The articles were identified using both database searches (e.g., Web of Science, Pub Med and Scifinder) using key words such as: antiviral activity, antiviral effects, lignans, HBV, HCV, HIV, HPV, HSV, JEV, SARS-CoV, RSV and influenza A virus, and directed searches of scholarly publisher’s websites including ACS, Elsevier, Springer, Thieme, and Wiley. The compounds were classified on their structural characteristics as 1) arylnaphthalene lignans, 2) aryltetralin lignans, 3) dibenzylbutyrolactone lignans, 4) dibenzylbutane lignans, 5) tetrahydrofuranoid and tetrahydrofurofuranoid lignans, 6) benzofuran lignans, 7) neolignans, 8) dibenzocyclooctadiene lignans and homolignans, and 9) norlignans and other lignoids. Details on isolation and antiviral activities of the most active compounds within each class of lignan are discussed in detail, as are studies of synthetic lignans that provide structure–activity relationship information.

Constituents of Bupleurum praealtum and Bupleurum veronense with Potential Immunomodulatory Activity.

In this investigation, chromatographic separations of the diethyl ether extracts of two European annual Bupleurum taxa, B. praealtum and B. veronense, yielded nine new natural products, namely, a series of esters of stereoisomeric tetradeca-5,7,9,11-tetraen-1-ols (1-4 and 8), a tetra-unsaturated γ-tetradecalactone (5), a dibenzylbutyrolactone lignan (7-oxoarcitin, 6), a falcarinol-related 17-membered macrolide (7) possessing a conjugated diyne-system, and an acylphloroglucinol derivative (9). All these new compounds were fully characterized by NMR, IR, UV, MS, and optical rotation measurement, including 1H NMR full spin spectral simulation, whereas the absolute configurations of 1, 5, and 9 were determined via chemical correlations and NMR analysis of Mosher esters. The in vitro potential immunomodulatory activities of 1, 4, 5, and (+)-arcitin were assessed by determining their effects on the functional properties of isolated rat splenocytes and peritoneal macrophages. The results obtained support the known immunomodulatory ethnomedicinal usage of Bupleurum species.

Metabolite Profiling by Hyphenated Liquid Chromatographic Mass Spectrometric Technique (HPLC-DAD-ESI-Q-TOF-MS/MS) and Neurobiological Potential of Haplophyllum sahinii and H. vulcanicum Extracts.

In the current study, the ethanol extracts of flower, stem, and root parts of two endemic Turkish species, e. g., Haplophyllum sahinii O. Tugay & D. Ulukuş and H. vulcanicum Boiss. & Heldr., were screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) associated with Alzheimer's disease as well as tyrosinase (TYR) linked to Parkinson's disease using ELISA microplate assay at 200 μg/mL. Among the extracts, the highest inhibition was caused by the stem extract of H. sahinii against BChE (IC50 =64.93±1.38 μg/mL). Consistently, all of the extracts were found to exert a selective inhibition towards BChE to some extent. It was only the root extract of H. vulcanicum that could inhibit AChE at low level (IC50 =203.18±5.33 μg/mL). None of the extracts displayed an inhibition over 50 % against TYR. Metabolite profiling of the extracts was achieved by a highly hyphenated liquid chromatographic mass spectrometric technique (HPLC-DAD-ESI-Q-TOF-MS/MS), which revealed the presence of furoquinoline (β-fagarine, γ-fagarine) and amide (tubasenicine, tubacetine) alkaloids; furano- (rutamarin), pyrano- (xanthyletine), and geranyloxy coumarins; phenylpropanoid (secoisolariciresinol), arylnaphthalene (mono-O-acetyldiphyllin apioside), and dibenzylbutyrolactone (kusunokinin, haplomyrfolin) lignans. Several important differences were observed between the extracts analyzed. β-Fagarine was the major alkaloid in H. vulcanicum, whereas γ-fagarine was present only in the roots of both Haplophyllum species; moreover, secoisolariciresinol and secoisolariciresinol dimethyl ether were the main lignans in the stems and flowers. This is the first study identifying ChE and TYR inhibitory effect and metabolic profiles of H. vulcanicum and H. sahinii.

Comprehensive Characterization of Lignans from Forsythia viridissima by UHPLC-ESI-QTOF-MS, and Their NO Inhibitory Effects on RAW 264.7 Cells

Lignans are known to be an important class of phenylpropanoid secondary metabolites. In the course of our studies on the chemodiversity of lignans, the necessity arose to develop a method for the fast detection and identification of bioactive lignan subclasses. In this study, we detected 10 lignan derivatives of different extracts of F. viridissima by UHPLC-ESI-QTOF-MS. Lignan glycosides (1 and 2), lignans (3 and 4), and lignan dimers (5–10) were identified by analysis of their exact masses and MSe spectra along with the characteristic mass fragmentation patterns and molecular formulas. We further investigated NO inhibitory effects of F. viridissima fractions and their major lignan derivatives to evaluate those anti-inflammatory effects. The methylene chloride fraction of F. viridissima as well as compounds 8 and 10 showed potent dose-dependent NO inhibitory effects on RAW 264.7 cells. Corresponding to the NO inhibition by compounds 8 and 10, lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) expression was notably reduced by both compounds. Our combined data with the bioactive results and the component analysis by UHPLC-ESI-QTOF-MS suggest that the methylene chloride fraction of F. viridissima roots could be potential anti-inflammatory agents and these are related to major lignans including dimeric dibenzylbutyrolactone lignans.

Lignans from the Twigs of Litsea cubeba and Their Bioactivities.

Litsea cubeba, an important medicinal plant, is widely used as a traditional Chinese medicine and spice. Using cytotoxicity-guided fractionation, nine new lignans 1–9 and ten known analogues 10–19 were obtained from the EtOH extract of the twigs of L. cubeba. Their structures were assigned by extensive 1D- and 2D-NMR experiments, and the absolute configurations were resolved by specific rotation and a combination of experimental and theoretically calculated electronic circular dichroism (ECD) spectra. In the cytotoxicity assay, 7′,9-epoxylignans with feruloyl or cinnamoyl groups (compounds 7–9, 13 and 14) were selectively cytotoxic against NCI-H1650 cell line, while the dibenzylbutyrolactone lignans 17–19 exerted cytotoxicities against HCT-116 and A2780 cell lines. The results highlighted the structure-activity relationship importance of a feruloyl or a cinnamoyl moiety at C-9′ or/and C-7 ketone in 7′,9-epoxylignans. Furthermore, compound 11 was moderate active toward protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 13.5 μM, and compounds 4–6, 11 and 12 displayed inhibitory activity against LPS-induced NO production in RAW264.7 macrophages, with IC50 values of 46.8, 50.1, 58.6, 47.5, and 66.5 μM, respectively.

Modular Synthesis and Biological Investigation of 5-Hydroxymethyl Dibenzyl Butyrolactones and Related Lignans.

Dibenzyl butyrolactone lignans are well known for their excellent biological properties, particularly for their notable anti-proliferative activities. Herein we report a novel, efficient, convergent synthesis of dibenzyl butyrolactone lignans utilizing the acyl-Claisen rearrangement to stereoselectively prepare a key intermediate. The reported synthetic route enables the modification of these lignans to give rise to 5-hydroxymethyl derivatives of these lignans. The biological activities of these analogues were assessed, with derivatives showing an excellent cytotoxic profile which resulted in programmed cell death of Jurkat T-leukemia cells with less than 2% of the incubated cells entering a necrotic cell death pathway.

Chemical constituents of Trachelospermum dunnii (H.Lév.) H.Lév.

Phytochemical investigation on the aerial parts of Trachelospermum dunnii led to the isolation and identification of 16 compounds, including nine dibenzylbutyrolactone lignans (1–9), two furanoid lignans (10–11), one dihydrobenzofuran lignan (12), one aryltetralin lignan (13), two flavonoids (14–15), and one phenolic compound (16). The structure of compound 1 was elucidated by means of spectroscopic analyses, including HRESIMS, and 1D and 2D NMR experiments. Compounds 1–16 are reported from title plant for the first time, while compounds 1–2, 10–12, and 14–16 have not been recorded previously in genus Trachelospermum. The dibenzylbutyrolactone lignans may serve as chemotaxonomic markers of T. dunnii.

Arctigenin protects against liver injury from acute hepatitis by suppressing immune cells in mice

As a phenylpropanoid and dibenzylbutyrolactone lignan present in medical plants, such as those used in traditional Chinese herbal medicine, including Arctium lappa (Niubang), arctigenin exhibits antimicrobial, anti-inflammatory, and anticancer activities. In this study, we investigated the protective role of arctigenin in Concanavalin A (ConA)-induced acute hepatitis in mice. Arctigenin remarkably reduced the congestion and necroinflammation of livers, and improved hepatic function (ALT and AST) in ConA-induced acute hepatitis in vivo. The infiltration of CD4 T, NKT and macrophages into the livers was found to be reduced with arctigenin treatment. Arctigenin suppressed ConA-induced T lymphocyte proliferations that might have resulted from enhanced IL-10 production by macrophages and CD4 T cells. These results suggested that arctigenin could be a powerful drug candidate for acute hepatitis through immune suppression.

Two new lignans from Horsfieldia kingii

Two new dibenzylbutyrolactol lignans and three known dibenzylbutyrolactone lignans were isolated from the twigs and leaves of Horsfieldia kingii. Their structures were elucidated by spectroscopic analysis. Cytotoxicity evaluation of these compounds against five human tumour lines showed no inhibitory effects.