During our phytochemical investigation of Haplophyllum villosum (Rutaceae), a perennial herb from Iran, a new 4,8-diaryl-3,7-dioxobicyclo-(3,3,0)-octane type lignan, eudesmin A (1), together with four known compounds--eudesmin (2), haplamine (3), umbelliferone (4) and scopoletin (5)--were isolated from aerial parts of the plant. The structures of the compounds were elucidated using NMR spectral analysis (¹H-NMR, ¹³C-NMR, HSQC, COSY and HMBC) as well as UV, IR and MS spectra and comparison with previously reported data.
New (-)-5',6-dimethoxyisolariciresinol-(3″,4″-dimethoxy)-3α-O-β-d-glucopyranoside compound was isolated from the methanol extract of the bark of Aglaia eximia (Meliaceae). The chemical structure of the new compound were elucidated on the basis of spectroscopic data including, UV, IR, HR-ESI-TOFMS, 1D-NMR, 2D-NMR and comparison with those related compounds previously reported.
A new and simple analytical method using HPLC with fluorescence detection was developed for the simultaneous determination of four lignans (phyllanthin, hypophyllanthin, phyltetralin and niranthin) in Phyllanthus niruri L. plant samples. Optimal separation was achieved with an isocratic mobile phase consisting of acetonitrile-water (55:45 v/v). The method recorded limits of detection (S/N=5) for phyllanthin at 0.61 ng/mL, hypophyllanthin at 6.02 ng/mL, phyltetralin at 0.61 ng/mL and niranthin at 1.22 ng/mL, being 80, 8, 80 and 40 times, respectively, lower when compared with those derived using HPLC-UV detection. The limits of quantification (S/N=12) were 4.88 ng/mL for phyllanthin and phyltetralin, 9.76 ng/mL for niranthin and 24.4 ng/mL for hypophyllanthin showing 40, 8 and 20 times, respectively, lower than those from the UV detection method. The within-day and between-day accuracy for the four lignans were between 98.1% and 102.9% while their precision values were below 2.2%. The mean recovery was between 92.5% and 110.1%. The method was then successfully applied for the quantification of lignans in P. niruri plant samples. The highest amount of lignans was found in the leaves followed by fruits, branches and stem, whilst the roots have the least amount of lignans.
The extract of Cinnamomum microphyllum showed strong antioxidant activity when it was tested against auto-oxidation of linoleic acid, superoxide, and DPPH radical scavenging activity. Further detailed investigations of the plant constituents and bioactivity studies led to the isolation and identification of known compounds consisting of three lignans, a coumarin, an ester and β-sitosterol. The structures of the compounds were determined using detailed spectroscopic analysis. The lignans were found to possess a significant antioxidant activity when tested against the three assay systems.
Standardized extract of Phyllanthus amarus has previously been shown to have a strong inhibitory effect on phagocytic activity of human neutrophils. The current study was carried out to evaluate the effects of constituents of the extract of P. amarus on nitric oxide (NO) production as well as lymphocyte proliferation and cytokine release from phagocytes. Three compounds, ethyl 8-hydroxy-8-methyl-tridecanoate, 7β,19α dihydroxy-urs-12-ene, and 1,7,8-trihydroxy-2-naphtaldehyde, together with seven known compounds were isolated from the whole plant of P. amarus. The isolated compounds and reference standards, ie, gallic acid, ellagic acid, corilagin, and geraniin, which were quantitatively analyzed in the extracts, were evaluated for their effects on immune cells. Among the compounds tested, the lignans, especially phyltetralin and phyllanthin, showed strong inhibition on lymphocyte proliferation with half maximal inhibitory concentration (IC50) values of 1.07 μM and 1.82 μM, respectively. Ethyl 8-hydroxy-8-methyl-tridecanoate and 1,7,8-trihydroxy-2-naphtaldehyde exhibited strong inhibition on nitric oxide production with IC50 values of 0.91 μM and 1.07 μM, respectively. Of all the compounds, corilagin was the strongest inhibitor of tumor necrosis factor-α release with an IC50 value of 7.39 μM, whereas geraniin depicted the strongest inhibitory activity on interleukin-1β release with an IC50 value of 16.41 μM. The compounds constituting the extract of P. amarus were able to inhibit the innate immune response of phagocytes at different steps.
The ethyl acetate and methanol bark extracts of Melicope glabra were evaluated for their antioxidant capacities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and β-carotene bleaching/linoleic acid system. Both extracts exhibited strong inhibition against the DPPH radical (IC50 values of 24.81 and 13.01 μg ml(-1), respectively) and strong antioxidant activity in β-carotene bleaching assay. Both samples were found to have high phenolic content with values of 39 and 44 mg GAE/g as indicated by Follin-Ciocalteau's reagent. Antioxidant TLC assay-guided isolation on the methanol extract led to the isolation of a new pyranocoumarin, glabranin (1), umbelliferone (2), scopoletin (3) and sesamin (4), and their structures were determined by spectroscopy. Compounds (1-3) showed significant activities on DPPH free radical with the IC50 of 240.20, 810.02 and 413.19 μg ml(-1), respectively. However, in β-carotene bleaching assay, sesamin (4) showed higher inhibitory activity (1 mg ml(-1), 95%) than glabranin (1) (1 mg ml(-1), 74%), whilst umbelliferone (2) and scopoletin (3) were slightly pro-oxidant.
A new naturally occurring dibenzylbutyrolactone lignan named isocubebinic ether has been isolated from Knema patentinervia. The structure was established by spectroscopic methods, which include Ultraviolet, Infrared, Nuclear Magnetic Resonance and Mass Spectrometry. The compound showed activity in the stimulation of glucose uptake by 3T3-L1 adipocytes.
A simple analytical method using HPLC with fluorescence detection was developed for the simultaneous determination of four lignans, phyllanthin (1), hypophyllanthin (2), phyltetralin (3) and niranthin (4) from Phyllanthus niruri L. in plasma. The method recorded limits of detection for 1, 2, 3 and 4 as 1.22, 6.02, 0.61 and 1.22 ng/ml, respectively, at a signal-to-noise ratio of 5:1 whereas their limits of quantification were 4.88, 24.41, 4.88 and 9.76 ng/ml, respectively, at a signal-to-noise ratio of 12:1. These values were comparable to those of other sensitive methods such as gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography-MS (HPLC-MS) and HPLC-electrochemical detection (HPLC-ECD) for the analysis of plasma lignans. A further advantage over known methods was its simple protocol for sample preparation. The within-day and between-day accuracies for the analysis of the four lignans were between 87.69 and 110.07% with precision values below 10.51%. Their mean recoveries from extraction were between 91.39 and 114.67%. The method was successfully applied in the pharmacokinetic study of lignans in rats. Following intravenous administration, the lignans were eliminated slowly from the body with a mean clearance of 0.04, 0.01, 0.03 and 0.02 l/kg h and a mean half-life of 3.56, 3.87, 3.35 and 4.40 h for 1, 2, 3 and 4, respectively. Their peak plasma concentration upon oral administration was 0.18, 0.56, 0.12 and 0.62 microg/ml, respectively, after 1h. However, their absorption was incomplete with a calculated absolute oral bioavailability of 0.62, 1.52, 4.01 and 2.66% for 1, 2, 3 and 4, respectively.
A number of three LC-MS/MS hybrid systems (QTof, TripleTof and QTrap) has been used to profile small metabolites (m/z 100-1000) and to detect the targeted metabolites such as quassinoids, alkaloids, triterpene and biphenylneolignans from the aqueous extracts of Eurycoma longifolia. The metabolite profiles of small molecules showed four significant clusters in the principle component analysis for the aqueous extracts of E. longifolia, which had been collected from different geographical terrains (Perak and Pahang) and processed at different extraction temperatures (35°C and 100°C). A small peptide of leucine (m/z 679) and a new hydroxyl methyl β-carboline propionic acid have been identified to differentiate E. longifolia extracts that prepared at 35°C and 100°C, respectively. From the targeted metabolites identification, it was found that 3,4ɛ-dihydroeurycomanone (quassinoids) and eurylene (squalene-type triterpene) could only be detected in the Pahang extract, whereas canthin-6-one-3N-oxide could only be detected in the Perak extract. Overall, quassinoids were present in the highest concentration, particularly eurycomanone and its derivatives compared to the other groups of metabolites. However, the concentration of canthin-6-one and β-carboline alkaloids was significantly increased when the roots of the plant samples were extracted at 100°C.
Bioassay (P388 lymphocytic leukemia cell line and human tumor cell lines)-guided separation of the extracts prepared from the tropical and coastal trees Hernandia peltata (Malaysia) and Hernandianymphaeifolia (Republic of Maldives) led to the isolation of a new lignan designated as hernanol (1) and 12 previously known lignans: (-)-deoxypodophyllotoxin (2), deoxypicropodophyllin (3), (+)-epiaschantin (4), (+)-epieudesmin (5), praderin (6), 5'-methoxyyatein (7), podorhizol (8), deoxypodorhizone (9), bursehernin (10), kusunokinol (11), clusin (12), and (-)-maculatin (13). The oxidative cyclization (with VOF(3)) of lignans 8, 9, and 10 resulted in a new and unusual benzopyran (14), isostegane (15), and a new dibenzocyclooctadiene lactone (16), respectively. The structure and relative stereochemistry of hernanol (1) and lignans 3, 7, 8, 9, 10, 11, and 12 were determined by 1D and 2DNMR and HRMS analyses. The structures and absolute stereochemistry of structures 2, 4, 5, 6, 13, 14, 15, and 16 were unequivocally determined by single-crystal X-ray diffraction analyses. Evaluation against the murine P388 lymphocytic leukemia cell line and human tumor cell lines showed podophyllotoxin derivatives 2 and 3 to be strong cancer cell line growth inhibitors and substances 4, 5, 8, and 15 to have marginal cancer cell line inhibitory activities. Seven of the lignans and one of the synthetic modifications (14) inhibited growth of the pathogenic bacterium Neisseria gonorrhoeae.
Linum usitatissimum commonly known as flaxseed is one of the oldest crops traditionally cultivated
mainly for its oil purposes. Flaxseed is widely known for its rich source of nutritive and bioactive compounds. Recently, it has gained considerable interest due to the potential health benefits attributed to its component of metabolites, including its antimicrobial properties. Two main components of flaxseed, the unsaturated fatty acids and lignan, are suggested as the main metabolites that exhibit antimicrobial activities. This paper aims to give an overview on fatty acid and phenolic compound in flaxseed and their possible activities as antimicrobial agents.
The methanol extract from the leaves of Phyllanthus niruri L. showed oral antihyperuricemic activity in potassium oxonate- and uric acid-induced hyperuricemic rats. Fractionation of the extract by resin chromatography led to the isolation of a less polar fraction which exhibited the highest reduction of plasma uric acid. Further antihyperuricemic-guided purification of the fraction afforded three lignans, phyllanthin (1), hypophyllanthin (2) and phyltetralin (3), of which 1 significantly reversed the plasma uric acid level of hyperuricemic animals to its normal level in a dose-dependent manner, comparable to that of allopurinol, benzbromarone and probenecid which are used clinically for the treatment of hyperuricemia and gout. Thus, the lignans of P. niruri are potential antihyperuricemic agents worthy of further investigation.
Matched MeSH terms: Lignans/administration & dosage; Lignans/pharmacology; Lignans/therapeutic use
In many developing countries, jaundice is the common symptom of hepatic diseases which are a major cause of mortality. The use of natural product-based therapies is very popular for such hepatic disorders. A great number of medicinal plants have been utilized for this purpose and some facilitated the discovery of active compounds which helped the development of new synthetic drugs against jaundice. However, more epidemiological studies and clinical trials are required for the practical implementation of the plant pharmacotherapy of jaundice. The focus of this second part of our review is on several of the most prominent plants used against jaundice identified in the analysis performed in the first part of the review viz. Andrographis paniculata (Burm.f.) Nees, Silybum marianum (L.) Gaertn., Terminalia chebula Retz., Glycyrrhiza glabra L. and some species of genus Phyllanthus. Furthermore, we discuss their physiological effects, biologically active ingredients, and the potential mechanisms of action. Some of the most important active ingredients were silybin (also recommended by German commission), phyllanthin and andrographolide, whose action leads to bilirubin reduction and normalization of the levels of relevant serum enzymes indicative for the pathophysiological status of the liver.
A new neolignan, 3,4-dimethoxy-3',4'-methylenedioxy-2,9-epoxy-6,7-cyclo-1,8-neolign-11-en-5(5H)-one, which has been named (+)-kunstlerone (1), together with six known alkaloids: (+)-norboldine (2), (+)-N-methylisococlaurine (3), (+)-cassythicine (4), (+)-laurotetanine (5), (+)-boldine (6) and (-)-pallidine (7), were isolated from the leaves of Beilschmiedia kunstleri. The structures were established through various spectroscopic methods notably 1D- and 2D-NMR, UV, IR and LCMS-IT-TOF. (+)- Kunstlerone (1) showed a strong antioxidant activity, with an SC(50) of 20.0 µg/mL.
The known lignan (-)-grandisin [1] has been isolated from Cryptocarya crassinervia by using the brine shrimp lethality test to direct the isolation; its structure and relative stereochemistry have been determined by ir, 1H nmr, ms, and X-ray crystallography as an all-trans alpha, alpha'-diaryl-beta, beta'-dimethyltetrahydrofuran. Compound 1 is not significantly cytotoxic in our panel of human tumor cells.
Phyllanthin and related lignans were found to be responsible, at least in part, for most of the activity of Phyllanthus species. This observation encouraged the authors to develop methods for the preparation of an extract rich in phyllanthin and related lignans from the aerial parts of P. niruri L. Direct extraction with solvents produced extracts with variable yields and contents of lignans. Lignans were identified by LC-ESI-MS analysis as phyllanthin (used as marker substance), hypophyllanthin, phylltetralin, nirtetralin, and niranthin. Extraction with boiling water produced 18.10 g% (w/w) extract with a trace amount of lignans (phyllanthin content of 0.33 ± 0.10 mg/g extract), while extraction with MeOH gave 3.6 g% w/w extract with a low phyllanthin content (3.1 mg/g extract), as determined by HPLC. However, Soxhlet extraction with hexane, CH2Cl2, or acetone gave extracts with low yields (0.82, 1.12, and 3.40 g% w/w, respectively) and a higher phyllanthin contents (36.2 ± 2.6, 11.7 ± 1.68, and 11.7 ± 1.10 mg/g extract, respectively). Extraction quality and efficiency were optimized by adopting the following three different approaches: (1) Alkaline digestion of the plant material with 30% potassium hydroxide yielded 3.1 g% w/w of purified extract with high phyllanthin content (22.34 ± 0.13 mg/g); (2) microwave-assisted extraction using 80% MeOH gave an extract with a better yield (8.13 g% w/w) and phyllanthin content (21.2 ± 1.30 mg/g) (after filtration through a Diaion HP-20 column); and (3) treatment of the ground plant material at 50 °C with two hydrolytic enzymes, cellulase (9 U/g for 12 h) and then, protease (4 U/g up to 72 h) optimized the yield of extract (13.92 g% w/w) and phyllanthin content (25.9 mg/g extract and total lignans content of 85.87 mg/g extract). In conclusion, the nonconventional methods presented here are superior for optimizing the yield of extract and its lignan contents from the aerial parts of P. niruri.
Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.
Hispidacine, an 8,4'-oxyneolignan featuring incorporation of an unusual 2-hydroxyethylamine moiety at C-7, and hispiloscine, a phenanthroindolizidine alkaloid, were isolated from the stem-bark and leaves of the Malaysian Ficus hispida Linn. Their structures were established by spectroscopic analysis. Hispidacine induced a moderate vasorelaxant activity in rat isolated aorta, while hispiloscine showed appreciable antiproliferative activities against MDA-MB-231, MCF-7, A549, HCT-116 and MRC-5 cell lines.
Zanthoxylum rhetsa is an aromatic tree, known vernacularly as "Indian Prickly Ash". It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin), a berberine alkaloid (columbamine) and a triterpenoid (lupeol) from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells.