lignans and medioresinol

Brain microvascular endothelial cells (BMVECs), as the important structure of blood-brain barrier (BBB), play a vital role in ischemic stroke. Pyroptosis of different cells in the brain may aggravate cerebral ischemic injury, and PGC-1α plays a major role in pyroptosis. However, it is not known whether BMVECs undergo pyroptosis after ischemic stroke and whether PGC-1α activator Medioresinol (MDN) we discovered may be useful against pyroptosis of endothelial cells and ischemic brain injury.. For in vitro experiments, the bEnd.3 cells and BMVECs under oxygen and glucose-deprivation (OGD) were treated with or without MDN, and the LDH release, tight junction protein degradation, GSDMD-NT membrane location and pyroptosis-associated proteins were evaluated. For in vivo experiments, mice underwent transient middle cerebral artery occlusion (tMCAO) for ischemia model, and the neuroprotective effects of MDN were measured by infarct volume, the permeability of BBB and pyroptosis of BMVECs. For mechanistic study, effects of MDN on the accumulation of phenylalanine, mitochondrial reactive oxygen species (mtROS) were tested by untargeted metabolomics and MitoSOX Red probe, respectively.. BMVECs underwent pyroptosis after ischemia. MDN dose-dependently activated PGC-1α, significantly reduced pyroptosis, mtROS and the expressions of pyroptosis-associated proteins (NLRP3, ASC, cleaved caspase-1, IL-1β, GSDMD-NT), and increased ZO-1 and Occludin protein expressions in BMVECs. In tMCAO mice, MDN remarkably reduced brain infarct volume and the permeability of BBB, inhibited pyroptosis of BMVECs, and promoted long-term neurobehavioral functional recovery. Mechanistically, MDN promoted the interaction of PGC-1α with PPARα to increase PPARα nuclear translocation and transcription activity, further increased the expression of GOT1 and PAH, resulting in enhanced phenylalanine metabolism to reduce the ischemia-caused phenylalanine accumulation and mtROS and further ameliorate pyroptosis of BMVECs.. In this study, we for the first time discovered that pyroptosis of BMVECs was involved in the pathogenesis of ischemic stroke and MDN as a novel PGC-1α activator could ameliorate the pyroptosis of endothelial cells and ischemic brain injury, which might attribute to reduction of mtROS through PPARα/GOT1 axis in BMVECs. Taken together, targeting endothelial pyroptosis by MDN may provide alternative therapeutics for brain ischemic stroke.

Topics: Animals; Aspartate Aminotransferase, Cytoplasmic; Chromatin Immunoprecipitation; Disease Models, Animal; Endothelium, Vascular; Fluorescent Antibody Technique; Gas Chromatography-Mass Spectrometry; HEK293 Cells; Humans; Ischemic Stroke; Lignans; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred ICR; Neuroprotective Agents; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; PPAR alpha; Pyroptosis; Rats, Sprague-Dawley

Activity-guided fractionation for complement inhibitors led to the isolation of 24 known compounds from Anchusa italica. Chemical types include eight megastigmane compounds, five triterpenoid compounds, five lignan compounds, three flavonoid compounds, two alkaloid compounds and one phenthyl alcohol compound. Among which, a lignan (medioresinol), an alkaloid (5-hydroxypyrrolidin-2-one) and a flavonoid (5-hydroxyl-3', 4', 6, 7-tetramethoxy flavone) exhibited better anticomplementary effects with CH

Topics: Animals; Boraginaceae; Complement Inactivator Proteins; Drug Evaluation, Preclinical; Erythrocytes; Flavonoids; Lignans; Medicine, Chinese Traditional; Molecular Structure; Pyrrolidinones; Sheep

Sixteen lignanoids were isolated from an aqueous extract of the commonly used Chinese traditional medicine Dangshen, the dried roots of Codonopsis pilosula, by using a combination of various chromatographic techniques, including silica gel, macroporous adsorbent resin, MCI resin, sephadex LH-20, and reversed phase semi-preparative HPLC. On the basis of spectral data analysis, their structures were elucidated and identified as（-）-（7R,7’R,8R,8’S）-4,4’-dihydroxy-3,3’,5,5’,7-pentamethoxy-2,7’-cyclolignane（1）,（-）-（7R,8S）- dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranosyl-（1’’’→2’’）-β-D-glucopyranoside（2）,（-）-（7R,8S）- dihydrodehydrodiconiferyl alcohol（3）,（+）-（7S,8R）-dehydrodiconiferyl alcohol（4）,（+）-balanophonin（5）,（+）- demethoxypinoresinol（6）,（+）-pinoresinol（7）,（+）-epipinoresinol（8）,（-）-syringaresinol（9）,（-）-medioresinol（10）,（-）-lariciresinol（11）,（-）-secoisolariciresinol（12）,（-）-ent-isolariciresinol（13）,（+）-（7S,8S）-3-methoxy-3’,7- expoxy-8,4’-neolignan-4,9,9’-triol（14）,（+）-（7S,8R）-3’,4-dihydroxy-3-methoxy-8,4’-neolignan（15）, and（-）-（7R,8R）-3’,4-dihydroxy-3-methoxy-8,4’-neolignan（16）. All these compounds were isolated from C. pilosula for the first time, while compound 1 is a new natural product of 2,7’-cyclolignan and 2 is a new 4’,7-epoxy- 8,3’-neolignan diglucoside. Compound 12 showed activity against Fe(2+)-cysteine induced rat liver microsomal lipid peroxidation with an inhibition ratio of（63.4 ± 8.3） % at 1×10(-5) mol·L(-1).

Topics: Animals; Butylene Glycols; Codonopsis; Drugs, Chinese Herbal; Furans; Lignans; Microsomes, Liver; Molecular Structure; Plant Extracts; Plant Roots; Rats

To study the chemical constituents from Serissa japonica.. The constituents were isolated by various chromatographic techniques and their structures were determined on the basis of spectroscopic data,as well as literatures.. Eleven compounds were obtained and identified as 3-hydroxy-1,2-dimethoxyanthraquinone( 1),1,2,4-trimethoxy-3-hydroxy-6-methyl anthraquinone( 2),emodin( 3),pinoresinol( 4),medioresinol( 5),( 7S,8R)-balanophonin-4-O-β-D-glucopyranoside( 6),lupeol( 7),icariside F2( 8),gallic acid( 9),methyl caffeate( 10) and 4-hydroxy-3-methoxyphenyl-β-D-glucopyranoside( 11).. Compounds 4and 5 are isolated from this plant for the first time,compounds 1 ~ 3 and 6 ~ 11 are isolated from Serissa genus for the first time.

Topics: Drugs, Chinese Herbal; Furans; Lignans; Rubiaceae

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; CHO Cells; Cinnamomum zeylanicum; Cricetinae; Cricetulus; Enzyme Inhibitors; Inhibitory Concentration 50; Lignans; Plant Bark; Plant Extracts; Plant Stems

To study the chemical constituents of stem of Camellia oleifera.. The chemical constituents were isolated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis.. Seven compounds were isolated from the stem of Camellia oleifera, whose structures were elucidated as (-) -pinoresinol (1), (-) -medioresinol (2), skullcapflavone II (3), betulinic acid (4), ursolic acid (5), 3-O-β-D-glucopyranosyl- (1 --> 2) -β-D-xylopyransoyl-(1 --> 3) -[β-D-glucopyranosyl- (1 --> 2)] -β-D-glucuronopyranosyl-22α-angeloyloxyolean-12-ene-15α,16α,28-triol (6) and oleanolic acid (7).. Compounds 1 - 6 are isolated from this plant for the first time, and compounds 1 - 3 are isolated from this genus for the first time.

Topics: Betulinic Acid; Camellia; Drugs, Chinese Herbal; Flavonoids; Furans; Lignans; Oleanolic Acid; Pentacyclic Triterpenes; Phytochemicals; Plant Stems; Plants, Medicinal; Triterpenes; Ursolic Acid

To investigate the chemical constituents of Selaginella sinensis (Desv.) Spring.. Chromatographic separations on Diaion HP-20, silica gel, and Sephadex LH-20 were used. The structures of the isolates were elucidated on the basis of spectroscopic analysis, as well as chemical methods.. Eight compounds were obtained and their structures were identified as sinensioside A (1), syringaresinol-4- O-β-D-glucopyranoside (2), (+)-medioresinol-4-O-β-D-glucopyranoside (3), pinoresinol-4, 4'-di-O-β-D-glucopyranoside (4), quercetin (5), eucomic acid (6), shikimic acid (7), and 2, 3-dihydroamentoflavone (8).. Compound 1 is a new dihydrobenzofuran sesquilignan glycoside from Selaginella sinensis.

Topics: Benzofurans; Furans; Glucosides; Lignans; Molecular Structure; Plant Extracts; Plant Stems; Quercetin; Selaginellaceae

One alkyl glycoside, saussurostelloside A (1), two phenolic glycosides, saussurostellosides B1 (2) and B2 (3), and 27 known compounds, including eleven flavonoids, seven phenolics, six lignans, one neolignan, one phenethyl glucoside and one fatty acid, were isolated from an ethanol extract of Saussurea stella (Asteraceae). Their structures were elucidated by NMR, MS, UV, and IR spectroscopic analysis. Of the known compounds, (+)-medioresinol-di-O-β-D-glucoside (7), picraquassioside C (10), and diosmetin-3'-O-β-D-glucoside (27) were isolated from the Asteraceae family for the first time, while (+)-pinoresinol-di-O-β-D-glucoside (6), di-O-methylcrenatin (11), protocatechuic acid (14), 1,5-di-O-caffeoylquinic acid (17), formononetin (28), and phenethyl glucoside (29) were isolated from the Saussurea genus for the first time. The anti-inflammatory activities of three new compounds (1-3), five lignans ((-)-arctiin (4), (+)-pinoresinol-4-O-β-D-glucoside (5), (+)-pinoresinol-di-O-β-D-glucoside (6), (+)-medioresinol-di-O-β-D-glucoside (7) and (+)-syringaresinol-4-O-β-D-glucoside (8)), one neolignan (picraquassioside C (10)), and one phenolic glycoside (di-O-methylcrenatin (11)) were evaluated by testing their inhibition of the release of β-glucuronidase from PAF-stimulated neutrophils. Only compound 5 showed moderate inhibition of the release of β-glucuronidase, with an inhibition ratio of 39.1%.

Topics: Animals; Anti-Inflammatory Agents; Coumaric Acids; Disaccharides; Female; Flavonoids; Furans; Glucosides; Glucuronidase; Glycosides; Hydroxybenzoates; Inflammation; Isoflavones; Lignans; Male; Molecular Structure; Neutrophils; Phytotherapy; Plant Extracts; Platelet Activating Factor; Quinic Acid; Rats, Wistar; Saussurea

In this study, antibacterial effects of (+)-Medioresinol isolated from stem bark of Sambucus williamsii and its synergistic activities in combination with antibiotics such as ampicillin, cefotaxime, and chloramphenicol were tested by antibacterial susceptibility testing and checkerboard assay. (+)-Medioresinol possessed antibacterial effects against antibiotics-susceptible- or antibiotics-resistant strains. Most of combinations between (+)-Medioresinol and each antibiotic showed synergistic interaction (fractional inhibitory concentration index ≤ 0.5) against bacterial strains including antibiotics-resistant Pseudomonas aeruginosa. Furthermore, the antibiofilm effect of (+)-Medioresinol alone or in combination with each antibiotic was investigated. The results indicated that not only (+)-Medioresinol but also its combination with each antibiotic had antibiofilm activities. It concludes that (+)-Medioresinol has potential as a therapeutic agent and adjuvant for treatment of bacterial infection.

Topics: Anti-Bacterial Agents; Biofilms; Cell Survival; Drug Synergism; Lignans; Pseudomonas aeruginosa; Sambucus

Higher intake of lignans, diphenolic plant compounds, may reduce the risk of certain types of cancer and cardiovascular diseases. We assessed the dietary intake of four lignans: matairesinol, secoisolariciresinol, lariciresinol and pinoresinol. Furthermore, for the breads we supplemented the data with two more lignans: syringaresinol and medioresinol. Study subjects were 172 men and 97 women aged 40-75 years, residing in Riga, the capital of Latvia, all living at home, eating habitual food. Median total lignan intake was 2259 (range 1169-5759) μg/day. Secoisolariciresinol contributed 58% and syringaresinol 22% of lignan intake. Bread was the major food source of lignans in men (86%), whereas in women it was bread (57%) and flaxseed (35%).

Topics: Adult; Aged; Bread; Butylene Glycols; Cardiovascular Diseases; Diet; Feeding Behavior; Female; Flax; Furans; Humans; Latvia; Lignans; Male; Middle Aged; Neoplasms; Phenols; Phytoestrogens; Plant Extracts; Sex Factors

The phytochemical (+)-Medioresinol, a furofuran type lignan identification and isolation on the stem bark of Sambucus williamsii, which is a folk medicinal plant used in traditional medicine. (+)-Medioresinol is known to possess a lesishmanicidal activity and cardiovascular disease risk reduction but its antifungal effects have not yet been identified. In this study, to confirm (+)-Medioresinol's antifungal properties and mode of action, we observed morphological and physiological change in Candida albicans. In cells exposed to (+)-Medioresinol, arrested the cell cycle and intracellular reactive oxygen species (ROS) which is a major cause of apoptosis were increased. The increase of ROS induced oxidative stress and the mitochondria dysfunction which causes release of pro-apoptotic factors. We investigated a series of characteristic cellular changes of apoptosis by using various apoptosis detection methods. We report here for the first time that (+)-Medioresinol has effects on mitochondria and induced the accumulation of ROS in C. albicans cells. We demonstrated that one of the important features of apoptosis, mitochondrial membrane depolarization is caused by ROS. Substantially, we investigated the release of cytochrome c, which is one of the factors of metacaspase activity. We also show that the effects of (+)-Medioresinol are mediated at an early stage in apoptosis acting on the plasma membrane phosphatidylserine externalization. In addition, (+)-Medioresinol induced apoptotic morphological changes, showing the reduced cell size (low FSC) and enhanced intracellular density (high SSC). In late stage of confirmation of diagnostic markers in yeast apoptosis include the effects of nucleus morphological change, DNA fragmentation and condensation by influence of oxidative stress. These apoptotic phenomena represent that oxidative stress and mitochondria dysfunctions by inducing the phytochemical (+)-Medioresinol must be an important factors of the apoptotic process in C. albicans. These results support the elucidation of the underlying antifungal mechanisms of (+)-Medioresinol.

Topics: Antifungal Agents; Apoptosis; Candida albicans; Cytochromes c; Lignans; Mitochondria; Mitochondrial Membranes; Oxidative Stress; Plant Bark; Plant Extracts; Reactive Oxygen Species; Sambucus

To investigate chemical constituents of Spatholobus suberectus Dunn.. Isolation and purification were carried out by column chromatographic methods. Compounds were characterized based on their physical characteristics and spectra data.. Seventeen compounds were isolated from ethanol extract of S. suberectus. The structures were elucidated as prestegane B (1), (2R, 3R)-buteaspermanol (2), (+)-medioresinol (3), (2R, 3R)-3,7-dihydroxyflavanone (4), benzeneethanol (5), 4, 7, 2'-trihydroxy-4'-methoxyisoflavanol (6), naringenin (7), blumenol A (8), protocatechuic acid ethyl ester (9), liquiritigenin (10), 7, 4'-dihydroxy-8-methoxy-isoflavone (11), 3, 5, 7, 3', 5'-pentahydroxyflavanone (12), protocatechuic acid (13), glycyroside (14), 8-methylretusin-7-O-β-D-glucopyranoside (15), 3, 3', 4', 5, 6, 7, 8-heptahydroxyflavan (16), and dulcisflavan (17).. All compounds are firstly isolated from the title plant and compounds 1, 3 were isolated from the Spatholobus genus for the first time.

Topics: 4-Butyrolactone; Fabaceae; Lignans; Molecular Structure; Plant Extracts

Two antileukemic daphnane esters, Pimelea factor P2 (I) and the new compound dircin (II), were isolated from the twigs and flowers of Dirca occidentalis A. Gray (Thymelaeaceae). Three lignans, (-)-medioresinol (III), (+)-syringaresinol (IV), and (-)-lariciresinol (V), as well as the coumarin daphnoretin (VI), were found to be additional cytotoxic constitents of this taxon.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Survival; In Vitro Techniques; Leukemia P388; Lignans; Mice; Plant Extracts